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Abstract  Diabetes mellitus (DM) is a complex disease that affects many systems. The most important cells of the immune system are lymphomononuclear (LMN) cells. Here, we aimed to evaluate the energy metabolism of LMN cells in patients with diabetes and impaired glucose tolerance. We measured LMN cell energy metabolism in patients with type 2 diabetes mellitus, impaired glucose tolerance (IGT) and healthy subjects. Cells were freshly isolated from peripheral blood and the subgroups were determined by flow cytometric method. Lactate production and glycogen utilization were significantly increased in the LMN cells of patients with type 2 DM and IGT when compared with healthy volunteers. No statistical difference was observed between the patients with type 2 DM and IGT. There was a significant correlation between fasting plasma glucose and lactate production in LMN cells. LMN cells changed their energy pathway in a diabetic state and preferred anaerobic glycolysis. Prediabetic range also affected energy metabolism in LMN cells. This abnormal energy production might cause dysfunction in LMN cells and the immune system in diabetic and prediabetic patients. In conclusion, we concluded that impaired glucose metabolism could change energy metabolism. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to determine the effects of Reiki on pain and biochemical parameters in patients undergoing bone marrow transplantation., Design: This research was a single-blind, repeated measures, randomized prospective controlled study., Method: This study was conducted between August 2022 and April 2023 with patients who underwent autologous in the bone marrow transplantation (BMT) unit. In the Reiki group (n = 21), Reiki therapy was applied directly to the energy centers for 30 min on the 0th and 1st day of BMT, and from a distance for 30 min on the 2nd day. No intervention was performed on the control group (n = 21). Data were collected using the Personal Information Form, Visual Analog Scale (VAS), and biochemical parameters. Pain and biochemical parameters were evaluated on days 0, 1, 2, and 10 before the Reiki application., Result: There were no statistically significant differences in pain scores between the groups before the intervention (p > .005). The Reiki group showed a significant improvement in the mean VAS score compared with the control group on days 1 and 2 (p = .002; p < .001, respectively). The measurement of procalcitonin showed a decrease in the Reiki group and an increase in the control group (p = .026, p = .001, p < .001, respectively). Although the Reiki group had better absolute neutrophil, thrombocyte, and C-reactive protein values than the control group, no significant difference was observed between the groups (p > .05)., Conclusion: Reiki is effective for pain control and enhancing the immune system response., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.)

Purpose: A head-to-head comparison of efficacy between a cyclin-dependent kinase 4/6 inhibitor plus endocrine therapy (ET) versus combination chemotherapy (CT) has never been reported in patients with clinically aggressive hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC)., Methods: In this open-label, multicenter, randomized phase II trial, pre/perimenopausal women with clinically aggressive HR+/HER2- ABC were randomly assigned 1:1 to first-line ribociclib (600 mg once daily; 3 weeks on, 1 week off) plus letrozole/anastrozole and goserelin or investigator's choice of combination CT (docetaxel plus capecitabine, paclitaxel plus gemcitabine, or capecitabine plus vinorelbine). The primary end point was progression-free survival (PFS)., Results: Among 222 patients randomly assigned to ribociclib plus ET (n = 112) or combination CT (n = 110), 150 (67.6%) had symptomatic visceral metastases, 41 (18.5%) had rapid disease progression per investigator's judgment, and 31 (14.0%) had symptomatic nonvisceral disease. Overall, 106 (47.7%) patients had investigator-assessed visceral crisis. The median follow-up time was 37.0 months. At data cutoff, 31.3% (ribociclib arm) and 15.5% (CT arm) of patients had completed study treatment and transitioned to post-trial access. The median PFS was 21.8 months (ribociclib plus ET; [95% CI, 17.4 to 26.7]) and 12.8 months (combination CT; [95% CI, 10.1 to 18.4); hazard ratio, 0.61 [95% CI, 0.43 to 0.87]; P = .003. The overall response rates and the median time to response in the ribociclib versus CT arms, respectively, were 66.1% and 61.8% and 4.9 months and 3.2 months (hazard ratio, 0.76 [95% CI, 0.55 to 1.06]). Lower rates of symptomatic adverse events were observed in the ribociclib versus CT arm., Conclusion: First-line ribociclib plus ET showed a significant PFS benefit, similar response rates, and better tolerability over combination CT in patients with clinically aggressive HR+/HER2- ABC.

Objective: We aimed to investigate response rates, survival analyses and factors affecting survival in patients with relapsed or refractory ovarian germ cell tumours who had previously received multiple lines of treatment, including high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT)., Methods: This study was designed as a cross-sectional, retrospective study., Results: Twenty-one patients were included. After HDC + ASCT, complete response (CR) was observed in 11 patients (52.3%), partial response (PR) in 3 patients (14.3%), stable disease (SD) in 3 patients (14.3%) and progressive disease (PD) in 4 patients (19.1%). TRM was observed in 1 patient. Median follow-up was 51.7 months. Median PFS and OS after HDC + ASCT were calculated to be 6.0 months and 14.8 months, respectively., Conclusions: Salvage HDC + ASCT is an effective option in the treatment of relapsed/refractory ovarian germ cell tumours, offering the potential for prolonged survival and cure., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To evaluate the efficacy and safety of nivolumab in the second-line (2L) or later-line (LL) treatment of patients with locally advanced/metastatic non-small cell lung cancer (NSCLC) in real-life setting in Türkiye., Methods: This study was designed as a national, multi-center, retrospective study. The study population was evaluated in two groups for the line of nivolumab therapy: those receiving nivolumab in the 2L (Group 2L) and third-line (3L) or LL (Group 3L/LL). Efficacy was evaluated based on one-year overall survival (OS) and progression-free survival (PFS). Safety was evaluated based on treatment-related adverse events (AEs) and nivolumab discontinuation rate., Results: Of 244 patients, 52.9% were in Group 2L and 47.1% were in Group 3L/LL. Demographic and clinical characteristics did not differ between the groups. In Group 2L and Group 3L/LL, one-year OS and PFS rates were 60.8% and 61.4% ( p  = 0.592) and 31.2% and 21.3% ( p  = 0.078), respectively. The objective response rate (ORR) was 34.7% in Group 2L and 27.3% in Group 3L/LL ( p  = 0.262). The percentage of patients reporting at least one AE in Groups 2L and 3L/LL was 34.9% and 43.5%, respectively ( p  = 0.169). Fatigue was the most common (16.4%) treatment-related AE in each group. The groups were comparable regarding the AE frequency. Nivolumab was discontinued in 61 patients in Group 2L and 53 patients in Group 3L/LL, with the most common reason being disease progression (57.4% and 66.0%, respectively)., Conclusion: Nivolumab is safe and effective in the 2L or 3L/LL treatment of locally advanced/metastatic NSCLC and associated with acceptable AEs in real-life setting.

Introduction: Data about the demographic and clinical characteristics of melanoma patients in Turkey is limited., Objectives: Data about the demographic and clinical characteristics of melanoma patients in Turkey is limited. We aimed to review the features of patients with primary cutaneous melanoma (PCM) diagnosed and treated in a tertiary referral center., Methods: The medical records of melanoma patients followed up by the Departments of Dermatology and Medical Oncology were retrospectively reviewed., Results: Within a 5-year period, 180 patients had been diagnosed with melanoma. Of all, 158 (87.8%) had PCM, 9 (5%) had mucosal melanoma, 9 (5%) had unknown primary melanoma, and 4 (2.2%) had ocular melanoma. Of 146 patients with PCM, 32.9% had stage I, 28.8% had stage II, 17.8% had stage III, and 20.5% had stage IV disease. The most common subtype was superficial spreading melanoma (38.8%). A statistically significant correlation was found between the patients Breslow thickness and lymph node involvement, histopathological subtype, and tumor ulceration (P < 0.001). Among all PCM patients, those in stage IV had the lowest 5-year survival rate when compared to the other disease stages (P < 0.001)., Conclusions: Relatively younger age at melanoma diagnosis, frequent presence of thick (> 4 mm) tumor, and frequent acral lentiginous subtype are the most remarkable features that suggest the low awareness and knowledge of melanoma in our population.

Introduction: Lenvatinib plus pembrolizumab was found to have antitumor activity and acceptable safety in previously treated metastatic NSCLC. We evaluated first-line lenvatinib plus pembrolizumab versus placebo plus pembrolizumab in metastatic NSCLC in the LEAP-007 study (NCT03829332/NCT04676412)., Methods: Patients with previously untreated stage IV NSCLC with programmed cell death-ligand 1 tumor proportion score of at least 1% without targetable EGFR/ROS1/ALK aberrations were randomized 1:1 to lenvatinib 20 mg or placebo once daily; all patients received pembrolizumab 200 mg every 3 weeks for up to 35 cycles. Primary end points were progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 and overall survival (OS). We report results from a prespecified nonbinding futility analysis of OS performed at the fourth independent data and safety monitoring committee review (futility bound: one-sided p < 0.4960)., Results: A total of 623 patients were randomized. At median follow-up of 15.9 months, median (95% confidence interval [CI]) OS was 14.1 (11.4‒19.0) months in the lenvatinib plus pembrolizumab group versus 16.4 (12.6‒20.6) months in the placebo plus pembrolizumab group (hazard ratio = 1.10 [95% CI: 0.87‒1.39], p = 0.79744 [futility criterion met]). Median (95% CI) PFS was 6.6 (6.1‒8.2) months versus 4.2 (4.1‒6.2) months, respectively (hazard ratio = 0.78 [95% CI: 0.64‒0.95]). Grade 3 to 5 treatment-related adverse events occurred in 57.9% of patients (179 of 309) versus 24.4% (76 of 312). Per data and safety monitoring committee recommendation, the study was unblinded and lenvatinib and placebo were discontinued., Conclusions: Lenvatinib plus pembrolizumab did not have a favorable benefit‒risk profile versus placebo plus pembrolizumab. Pembrolizumab monotherapy remains an approved treatment option in many regions for first-line metastatic NSCLC with programmed cell death-ligand 1 tumor proportion score of at least 1% without EGFR/ALK alterations., Competing Interests: Disclosure Dr. Yang reports receiving funding to institution for serving on advisory or consultancy services for Daiichi Sankyo, Eli Lilly, Merck KGaA, Darmstadt, Germany, Merck Sharp & Dohme, Novartis, Roche, Genentech, Takeda Oncology, Yuhan Pharmaceuticals, Janssen Pharmaceuticals, Puma Technology, Gilead Sciences Inc., GlaxoSmithKline, BeiGene, Blueprint Medicines Corporation, Regeneron Pharmaceutical, and Taiho Pharmaceutical; receiving grant from Roche/Genentech; and having advisory or consultancy services from Ono Pharmaceuticals and Pfizer. Dr. Han reports receiving study funding to the institution from Eisai Inc., Nutley, New Jersey, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, New Jersey, to support study conduct. Dr. Jiménez reports receiving study funding to the institution from Eisai Inc., Nutley, New Jersey, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, New Jersey, to support study conduct. Dr. Lee reports receiving study funding to the institution from Eisai Inc., Nutley, New Jersey, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, New Jersey, to support study conduct. Dr. Koralewski reports receiving study funding to the institution from Eisai Inc., Nutley, New Jersey, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, New Jersey, to support study conduct. Dr. Karadurmus reports receiving study funding to the institution from Eisai Inc., Nutley, New Jersey, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, New Jersey, to support study conduct. Dr. Sugawara reports receiving grants or contracts to their institution from AnHeart, AstraZeneca, Chugai Pharma, MSD, Daiichi Sankyo, Bristol-Myers Squibb, Nippon Boehringer Ingelheim, Ono Pharmaceuticals, AbbVie, Amgen, Taiho Pharmaceutical, Takeda, and Clinipace; payment or honoraria from AstraZeneca, Chugai Pharma, Ono Pharmaceutical, Bristol-Myers Squibb, MSD, Nippon Boehringer Ingelheim, Pfizer, Taiho Pharmaceutical, Eli Lilly and Company, Novartis, Kyowa Kirin, Takeda, Nippon Kayaku, Merck Biopharma Japan, Amgen, AbbVie, Otsuka, Thermo Fisher Scientific, and Towa Pharmaceutical. Dr. Livi reports receiving study funding to the institution from Eisai Inc., Nutley, New Jersey, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, New Jersey, to support study conduct. Dr. Basappa reports receiving grants or contracts from Ipsen; receiving payment or honoraria from Bayer, Astellas, and Janssen; receiving support for attending meetings from Eisa, Ipsen, and Janssen; having participation on data safety monitoring board or advisory board with Eisai, Ipsen, Pfizer, Bristol-Myers Squibb, Roche, Janssen, AstraZeneca, EMD Serono, Bayer, Astellas, and MSD. Dr. Quantin reports receiving payment or honoraria to their institution from Sanofi, Bristol-Myers Squibb, and AstraZeneca; receiving support for attending meetings from Janssen Cilag, Sanofi, and Pfizer; and having participation on data safety monitoring board or advisory board with Bristol-Myers Squibb. Dr. Dudnik reports receiving study funding to the institution from Eisai Inc., Nutley, New Jersey, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, New Jersey, to support study conduct. Dr. Moran reports receiving support for present manuscript from MSD; grants or contracts from Abbott; consulting fees from Bristol-Myers Squibb and MSD; honoraria from Bristol-Myers Squibb, MSD, AstraZeneca, GlaxoSmithKline, Novartis, and Bayer; support for attending meetings from Tecnofarma, Roche, Pfizer, Bayer, and Janssen; and having participation on data safety monitoring board or advisory board with MSD. Dr. Mekhail reports receiving payment for speakers bureau from MSD. Drs. Okpara and Dutcus are employees of Eisai Ltd., Hatfield, UK. Drs. Zimmer, Samkari, and Bhagwati are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, New Jersey, and own stock in Merck & Co., Inc., Rahway, New Jersey. Dr. Csőszi reports receiving study funding to the institution from Eisai Inc., Nutley, New Jersey, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, New Jersey, to support study conduct., (Copyright © 2024 Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Adrenocortical carcinoma (ACC) is a rare yet highly malignant tumor associated with significant morbidity and mortality. This study aims to delineate the clinical features, survival patterns, and treatment modalities of ACC, providing insights into the disease's prognosis., Materials and Methods: A retrospective analysis of 157 ACC patients was performed to assess treatment methodologies, demographic patterns, pathological and clinical attributes, and laboratory results. The data were extracted from the hospital's database. Survival analyses were conducted using the Kaplan-Meier method, with univariate and multivariate analyses being performed through the log-rank test and Cox regression analyses., Results: The median age was 45, and 89.4% had symptoms at the time of diagnosis. The median tumor size was 12 cm. A total of 117 (79.6%) patients underwent surgery. A positive surgical border was detected in 26 (24.1%) patients. Adjuvant therapy was administered to 44.4% of patients. The median overall survival for the entire cohort was 44.3 months. Median OS was found to be 87.3 months (95% confidence interval [CI] 74.4-100.2) in stage 2, 25.8 (95% CI 6.5-45.1) months in stage 3, and 13.3 (95% CI 7.0-19.6) months in stage 4 disease. Cox regression analysis identified age, Ki67 value, Eastern Cooperative Oncology Group performance status, and hormonal activity as significant factors associated with survival in patients with nonmetastatic disease. In metastatic disease, only patients who underwent surgery exhibited significantly improved overall survival in univariate analyses., Conclusion: ACC is an uncommon tumor with a generally poor prognosis. Understanding the defining prognostic factors in both localized and metastatic diseases is vital. This study underscores age, Ki67 value, Eastern Cooperative Oncology Group performance status, and hormonal activity as key prognostic determinants for localized disease, offering critical insights into the complexities of ACC management and potential avenues for targeted therapeutic interventions., Competing Interests: Disclosure The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

To evaluate radiological and clinical features in metastatic anaplastic lymphoma kinase+ non-small cell lung cancer patients and crizotinib efficacy in different lines. This national, non-interventional, multicenter, retrospective archive screening study evaluated demographic, clinical, and radiological imaging features, and treatment approaches in patients treated between 2013-2017. Totally 367 patients (54.8% males, median age at diagnosis 54 years) were included. Of them, 45.4% were smokers, and 8.7% had a family history of lung cancer. On radiological findings, 55.9% of the tumors were located peripherally, 7.7% of the patients had cavitary lesions, and 42.9% presented with pleural effusion. Pleural effusion was higher in nonsmokers than in smokers (37.3% vs. 25.3%, P = .018). About 47.4% of cases developed distant metastases during treatment, most frequently to the brain (26.2%). Chemotherapy was the first line treatment in 55.0%. Objective response rate was 61.9% (complete response: 7.6%; partial response: 54.2%). The highest complete and partial response rates were observed in patients who received crizotinib as the 2nd line treatment. The median progression-free survival was 14 months (standard error: 1.4, 95% confidence interval: 11.2-16.8 months). Crizotinib treatment lines yielded similar progression-free survival (P = .078). The most frequent treatment-related adverse event was fatigue (14.7%). Adrenal gland metastasis was significantly higher in males and smokers, and pleural involvement and effusion were significantly higher in nonsmokers-a novel finding that has not been reported previously. The radiological and histological characteristics were consistent with the literature data, but several differences in clinical characteristics might be related to population characteristics., Competing Interests: OUD and BA are the employees of Pfizer Biopharmaceuticals Group, Istanbul, Türkiye. BOU reports research support for clinical trials through institution from Novartis, GSK, Astra Zeneca; honoraria from BMS, Amgen, Novartis, Pfizer, Astra Zeneca, Roche, MSD; support for attending meetings from Roche, Pfizer, Novartis and is on the advisory boards of Takeda, Roche, Astra Zeneca, MSD, Novartis, Amgen, Gilead. ME has support funding for medical writing from Pfizer, provides lectures for Pfizer, Novartis, Roche, Astellas, Janssen, MSD, Gen, Nobel, Deva, Eczacibasi, BMS, Takeda, Astra Zeneca, has support for attending meetings from Roche, has participation on advisory board of Novartis, Pfizer, Roche, Astellas, MSD, Deva, Astra Zeneca. The remaining authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

According to current evidence, testing for germline BRCA pathogenic variants in newly diagnosed breast cancer (BC) patients has the potential to reduce the burden of the disease through targeted therapies and secondary prevention. A personalized approach to testing can lead to improved individual outcomes for patients. Despite the proven clinical utility and therapeutic impact of BRCA1/2 tests in shaping therapy for metastatic BC, awareness and access to these tests are limited in many developing countries, including Türkiye. This limitation impacts the healthcare economy as delayed or missed interventions can lead to increased long-term costs. The limited access is mainly due to fear of stigmatization among patients, country-specific legislation and costs, a lack of awareness, vagueness surrounding the tests and access restrictions. This review offers a perspective for policymakers and healthcare providers in Türkiye to establish pathways that integrate the patient experience into comprehensive care pathways and national cancer control plans.

Central nervous system (CNS) metastases can be seen at a rate of 30% in advanced stages for patients with non-small cell lung cancer (NSCLC). Growing evidence indicates the predictive roles of driver gene mutations in the development of brain metastases (BM) in recent years, meaning that oncogene-driven NSCLC have a high incidence of BM at diagnosis. Today, 3rd generation targeted drugs with high intracranial efficacy, which can cross the blood-brain barrier, have made a positive contribution to survival for these patients with an increased propensity to BM. It is important to update the clinical and pathological factors reflected in the survival with real-life data. A multi-center, retrospective database of 306 patients diagnosed with driver mutant NSCLC and initially presented with BM between between November 2008 and September 2022 were analyzed. The median progression-free survival (mPFS) was 12.25 months (95% CI, 10-14.5). While 254 of the patients received tyrosine kinase inhibitor (TKI), 51 patients received chemotherapy as first line treatment. The median intracranial PFS (iPFS) was 18.5 months (95% CI, 14.8-22.2). The median overall survival (OS) was 29 months (95% CI, 25.2-33.0). It was found that having 3 or less BM and absence of extracranial metastases were significantly associated with better mOS and iPFS. The relationship between the size of BM and survival was found to be non-significant. Among patients with advanced NSCLC with de novo BM carrying a driver mutation, long-term progression-free and overall survival can be achieved with the advent of targeted agents with high CNS efficacy with more conservative and localized radiotherapy modalities., (© 2024. The Author(s).)

Introduction: The optimal management of relapsed/refractory germ cell tumors remains unsettled. In this study, we aimed to evaluate the efficacy of high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) as salvage therapy in patients who progressed after at least one line of cisplatin-based chemotherapy., Methods: We retrospectively reported the results of 133 patients who underwent HDCT and ASCT as salvage therapy from 2016 to 2021. Patients received 3 cycles of paclitaxel, ifosfomide and cisplatin (TIP) regimen as induction and 1 cycle of carboplatin 700 mg/m2 on days 1-3 plus etoposide 750 mg/m2 on days 1-3, followed by ASCT. Demographic and clinicopathological features of patients, the International Germ Cell Cancer Collaborative Group (IGCCCG) risk group at diagnosis, serum alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (HCG) levels before HDCT, treatment-related complications and survival outcomes were recorded., Results: The median age of the patients was 31 (range 18-62). The median follow-up was 31.1 months (95% CI, 28.9-33.3 months). During the median follow-up period, 74 of the 133 patients were still alive, and 63 of these were in complete remission. The median progression-free survival (PFS) was 25.8 months (95% CI, 8.1-43.4 months). The 2-year PFS rate was 50.3% and the 2-year overall survival (OS) rate was 60.8%. Variables that remained statistically significant in multivariable analysis and were associated with poor prognosis were mediastinal primary tumor location, presence of brain metastases, and higher AFP and HCG levels at baseline., Conclusion: One course of HDCT and ASCT after induction with TIP is an effective and feasible treatment option for salvage treatment of relapsed/refractory germ cell tumors, with cure rates of up to 60%., (© 2024 S. Karger AG, Basel.)

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. The primary endpoints were the overall response (ORR) and disease control rate (DCR)., Results: The cohort's median age was 56, and 53.8% of the patients were male. The most frequent diagnosis was sarcoma (29%), and 81.7% of the patients were previously treated with at least one line of systemic therapy in the advanced stage. The ORR and DCR were 36.8% and 63.2%, respectively. The germ cell tumors had the lowest ORR (0%), while the Merkel cell carcinoma had the highest ORR to ICIs (57.1%). Patients treated with ICI + ICI or ICI plus chemotherapy combinations had higher ORR (55.2% vs. 27.6%, p = 0.012) and DCR (82.8% vs. 53.4%, p = 0.008). The median OS was 13.47 (95% CI: 7.79-19.15) months, and the six and 12-month survival rates were 71% and 52%. The median duration of response was 16.59 months, and the 12-month progression-free survival rate was 66% in responders. The median time-to-treatment failure was 5.06 months (95% CI: 3.42-6.71). Three patients had high-grade irAEs with ICIs (grade 3 colitis, grade 3 gastritis, and grade 3 encephalitis in one patient each)., Conclusion: We observed over 30% ORR and a 13-month median OS in patients with rare cancers treated with ICI monotherapy or ICI plus CT combinations. The response rates to ICIs or ICIs plus CT significantly varied across different tumor types. Responding patients had over 2 years of survival, highlighting a need for further trials with ICIs for patients with rare tumors., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

The use of tyrosine kinase inhibitors has made a breakthrough in the treatment of non-small-cell lung cancer (NSCLC). Recently, lorlatinib, a third-generation tyrosine kinase inhibitor, has demonstrated significant systemic and intracranial activity in both first-line and subsequent-line therapy in ALK-positive NSCLC patients. In this review, general characteristics of lorlatinib, its efficacy in the treatment of ALK-positive NSCLC patients and the safety of lorlatinib, particularly addressing central nervous system adverse events, are discussed. Management of central nervous system adverse events, which seem to be specific to lorlatinib therapy, is outlined.

Background: Most of the studies on salivary gland cancers are limited for various reasons such as being single-center, small number of patients, including only major or minor SGCs, or only including epidemiological data., Methods: A total of 37 medical oncology clinics from different regions of Turkey participated in this retrospective-multicenter study. The analyzed data included clinical and demographical features, primary treatment, metastasis localizations, and treatments and includes certain pathologic features., Results: The study included data from a total of 443 SGCs. 56.7% was in major salivary glands and 43.3% was in minor salivary glands. Distant metastasis in the major SGCs was statistically significantly more common than in the minor SGCs, locoregional recurrence was statistically significantly more common in the minor SGCs than in the major SGCs (p = 0.003)., Conclusions: Epidemiological information, metastasis and recurrence patterns, treatment modalities, and survival analysis of the patients over 20 years of follow-up are presented., (© 2023 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Background: In this study, we report real-world results from the 5-year follow-up data of urothelial carcinoma patients treated with immune checkpoint blockade therapies (ICTs)., Patients and Methods: Metastatic urothelial carcinoma patients treated with at least one course of ICT were included in the study. The primary endpoint was overall response rate (ORR), and secondary endpoints were overall survival (OS), progression-free survival (PFS), duration of treatment with ICT, and safety. Median follow-up, PFS, and OS were estimated by using the Kaplan-Meier method., Results: Data of 201 eligible patients were analyzed. The median age of the patients was 66 (37-86) years, and 156 (84.3%) were male. The majority of patients (94.6%) had Eastern Cooperative Oncology Group (ECOG) PS scores of 0 to 1 and primary tumor in the bladder was predominant (87.5%). The median follow-up time was 54 (1.15-65) months. The rate of complete response (CR) to ICT, partial response (PR) rate, and ORR were 10.4% (n = 21), 22.4% (n = 45), and 32.4% (n = 66), respectively. The median duration of response (DOR) was 34.8 months (95% confidence interval [CI], 29.2-42.1). Of the 66 patients who responded to treatment, 28 (42%) had an ongoing response at the time of the analysis. Median PFS and OS were 3.8 (2.6-5.8) months and 9.4 (7.4-11.4) months, respectively. The 5-year PFS and OS rates were 9.8% and 12.8%, respectively. Fifty-eight percent of patients experienced a treatment-related adverse event of any grade, and 33 (16.4%) patients had a grade 3 to 4 adverse event., Conclusion: This 5-year analysis of real-world data confirms the durable response and long-term survival with ICT in metastatic urothelial carcinoma patients., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction and Aim: Primary mediastinal B-cell lymphomas (PMBL) are aggressive B- cell lymphomas. Although the initial treatment models vary in PMBL, appropriate treatment methods are not known. We aim to show real-life data on health outcomes in adult patients with PMBL who received various type of chemoimmunotherapies in Turkey., Method: We analyzed the data of 61 patients who received treatments for PMBL from 2010 to 2020. The overall response rate (ORR), overall survival (OS) and progression-free survival (PFS) of the patients were evaluated., Results: 61 patients were observed in this study. The mean age of the study group was 38.4 ± 13.5 years. From among them, 49.2% of the patients were female (n = 30). For first-line therapy, 33 of them had received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen (54%). Twenty-five patients had received rituximab, etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (DA-EPOCH-R) regimen. The ORR was 77%. The median OS and PFS were as follows: 25 months (95% CI: 20.4-29.4) and 13 months (95% CI: 8.6-17.3), respectively. The OS and PFS at 12 months were 91.3% and 50%, respectively. The OS and PFS at five years were 64.9% and 36.7%, respectively. Median follow-up time period was 20 months (IQR 8.5-38.5)., Conclusion: R-CHOP and DA-EPOCH-R showed good results in PMBL. These remain one of the best determined systemic treatment options for first-line therapy. Also, the treatment was associated with good efficacy and tolerability.

Aim: To investigate the pathological complete response (pCR) achieved after neoadjuvant therapy with versus without adding pertuzumab (P) to trastuzumab (H) plus neoadjuvant chemotherapy (NCT) in HER2+ breast cancer (BC) patients in a real-life setting., Methods: A total of 1528 female HER2+ BC patients who received NCT plus H with or without P were included in this retrospective real-life study. Primary endpoint was pCR rate (ypT0/Tis ypN0). Clinicopathological characteristics, event-free survival (EFS) time, and relapse rates were evaluated with respect to HER2 blockade (NCT-H vs. NCT-HP) and pCR., Results: Overall, 62.2% of patients received NCT-H and 37.8% received NCT-HP. NCT-HP was associated with a significantly higher pCR rate (66.4 vs. 56.8%, p  < 0.001) and lower relapse (4.5 vs. 12.2%, p  < 0.001) in comparison to NCT-H. Patients with pCR had a significantly lower relapse (5.6 vs. 14.9%, p  < 0.001) and longer EFS time (mean(SE) 111.2(1.9) vs. 93.9(2.7) months, p  < 0.001) compared to patients with non-pCR. Patients in the NCT-HP group were more likely to receive docetaxel (75.0 vs. 40.6%, p  < 0.001), while those with pCR were more likely to receive paclitaxel (50.2 vs. 40.7%, p  < 0.001) and NCT-HP (41.5 vs. 32.1%, p  < 0.001). Hormone receptor status and breast conservation rates were similar in NCT-HP vs. NCT-H groups and in patients with vs. without pCR. Invasive ductal carcinoma (OR, 2.669, 95% CI 1.596 to 4.464, p  < 0.001), lower histological grade of the tumor (OR, 4.052, 95% CI 2.446 to 6.713, p  < 0.001 for grade 2 and OR, 3.496, 95% CI 2.020 to 6.053, p  < 0.001 for grade 3), lower T stage (OR, 1.959, 95% CI 1.411 to 2.720, p  < 0.001) and paclitaxel (vs. docetaxel, OR, 1.571, 95% CI 1.127 to 2.190, p  = 0.008) significantly predicted the pCR., Conclusions: This real-life study indicates that adding P to NCT-H enables higher pCR than NCT-H in HER2+ BC, while pCR was associated with lower relapse and better EFS time.

Background: Ribociclib, palbociclib and abemaciclib are currently approved CDK4/6 inhibitors along with aromatase inhibitors as the first-line standard-of-care for patients with hormone receptor-positive, HER2-negative metastatic breast cancer. Methods: The authors report retrospective real-life data for 600 patients with estrogen receptor- and/or progesterone receptor-positive and HER2-negative metastatic breast cancer who were treated with ribociclib and palbociclib in combination with letrozole. Results & conclusion: The results demonstrated that the combination of palbociclib or ribociclib with letrozole has similar progression-free survival and overall survival benefit in real life for the patient group with similar clinical features. Specifically, endocrine sensitivity may be a factor to be considered in the treatment preference.

Objective: Neuroendocrine neoplasms (NENs) originate from the diffuse neuroendocrine cell system and constitute a heterogeneous group of tumors exhibiting diverse clinical and biological characteristics. NENs include well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). In the present study, we performed a retrospective analysis of patients diagnosed with NET to evaluate clinicopathological characteristics, treatment and outcomes., Material and Methods: Data from 153 patients diagnosed with NET who were treated and followed up at three tertiary care centers from November 2002 to June 2021 were retrospectively evaluated. Clinicopathological and prognostic factors, treatment modalities and survival data were analyzed. Kaplan-Meier analysis was used to assess survival data and comparisons were performed using the logrank test., Results: Median age (IQR) was 53 (18-80) years. 85.6% of the patients had gastro-entero-pancreatic (GEP)-NET. The primary tumor was resected in 95 patients (62.1%) and metastasectomy were performed in 22 patients (14.4%). Seventy-eight patients received systemic therapy for metastatic disease. Patients were followed up for a median of 22 (IQR = 33.8) months. The estimated one-year and three-year survival rate was 89.8% and 74.4%, respectively. Median progression-free survival (PFS) were 10.1, 8.5, and 4.2 months after first-, second- and third-line therapy, respectively., Conclusion: The number of systemic treatment options and diagnostic tools for NETs has significantly improved in the last few years. NET classification, which treatment will be more appropriate for which group of patients, the molecular basis of this disease and the development of treatment strategies are open-ended questions that still need to be investigated.

Objectives: Advanced-stage biliary tract cancers (BTC) are rare malignancies with poor prognosis. There are few prospective trials, but several retrospective studies regarding treatment options. In this study, we aimed to investigate the role of systemic inflammatory parameters (SIP) and other possible independent factors that may affect survival and treatment approaches and to determine the benefit of later-line treatments in these patients., Methods: A total of 284 patients, initially diagnosed with advanced stage or progressed after curative treatment of BTC, from different oncology centers in Turkey were included in this retrospective study. The prognostic significance of clinicopathological factors, SIPs and treatment options was analyzed., Results: At a median follow-up of 13 months, the median progression-free survival (PFS) was 6.1 months (95% CI:5.51-6.82), and the median overall survival (OS) time was 16.8 months (95% CI: 13.9-19.6). Treatment choice ( p  < .001 HR:0.70 CI95% 0.55-0.9), performance status ( p  < .001 HR:2.74 CI 95% 2.12-3.54) and neutrophil-to-lymphocyte ratio (NLR) ( p  = .02 HR:1.38 CI 95% 1.03-1.84) were independent prognostic factors for PFS. For OS, the independent prognostic indicators were determined as The Eastern Cooperative Oncology Group Performance Status (ECOG PS) ( p  < .001 HR:1.78 CI 95% 1.5-2.3), Systemic Immune-inflammation Index (SII) ( p  < .001 HR:0.51 CI95% 0.36-0.73) and stage at diagnosis ( p  = .002 HR:1.79 CI 95% 1.24-2.59). Furthermore, second and third line treatments significantly prolonged OS in advanced BTC ( p  < .001 HR:0.55 CI 95% 0.38-0.79; p  = .007 HR:0.51 CI95% 0.31-0.83, respectively)., Conclusion: SII and NLR are useful prognostic factors and may be helpful in making treatment decisions. Additionally, second and later-line treatments in advanced BTC have a significant impact on survival under real-life conditions.

In our study, we aimed to evaluate the pathological response rates and side effect profile of adding pertuzumab to the treatment of HER2+ locally advanced, inflammatory, or early-stage breast cancer. This study was conducted by the Turkish Oncology Group (TOG) with data collected from 32 centers. Our study was multicentric, and a total of 364 patients were included. The median age of the patients was 49 years (18-85 years). Two hundred fifteen (60%) of the cases were hormone receptor/HER2+ positive(ER+ or PR+, or both), and 149 (40%) of them were HER2-rich (ER and PR negative). The number of complete responses was 124 (54%) in the docetaxel+trastuzumab+pertuzumab arm and 102 (45%) in the paclitaxel+trastuzumab+pertuzumab arm, and there was no difference between the groups in terms of complete response. In 226 (62%) patients with complete response, a significant correlation was found with DCIS, tumor focality, removed lymph node, and ER status P < 0.05. Anemia, nausea, vomiting, myalgia, alopecia, and mucosal inflammation were significantly higher in the docetaxel arm, P < 0.05. In our study, no statistical difference was found between the before-after echocardiography values. DCIS positivity in biopsy before neoadjuvant chemotherapy, tumor focality; the number of lymph nodes removed and ER status were found to be associated with pCR. In conclusion, we think that studies evaluating pCR-related clinicopathological variables and radiological imaging features will play a critical role in the development of nonsurgical treatment approaches., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To determine the survival endpoints and treatment-related adverse events after the use of the gemcitabine, paclitaxel, and oxaliplatin (GemPOx) protocol in relapsed/refractory germ cell tumours (GCTs) who had previously received multi-line systemic treatments including high-dose chemotherapy., Study Design: Observational study., Place and Duration of Study: Clinic of Medical Oncology, Gulhane School of Medicine, Ankara, Turkey, between January 2017 and August 2021., Methodology: Clinical characteristics of adult patients with relapsed/refractory GCTs treated with the GemPOx protocol were recorded from the hospital's patient registry database. Patients without a medical record were not included in the study. Objective response rate (ORR), progression-free survival (PFS), overall survival (OS), one-year PFS rate, one-year OS rate, and treatment-related haematological side effects were determined after GemPOx., Results: Fifty-three adult patients were included (47 of them were male). Seventy-eight percent had Stage 3 at initial diagnosis. Twenty-four percent of the patients received more than four lines of systemic chemotherapy. Ninety-six percent of the patients received high-dose chemotherapy prior to GemPOx. ORR, which is the sum of the complete and partial response rates, was 69.8%. PFS was determined as 8.5 ± 5.4 months. The one-year PFS rate was 30.3%. OS was 15.9 ± 10.6 months. The one-year OS rate was 72.6%. Febrile neutropenia was observed in 15.1% of the patients., Conclusion: In patients with relapsed/refractory GCTs receiving multi-line systemic chemotherapy, significant PFS and OS are achievable, and a manageable spectrum of haematological side effects is observed with GemPOx., Key Words: Gemcitabine, Paclitaxel, Oxaliplatin, Germ cell tumour.

Objective: To demonstrate the treatment responses, survival analysis, and treatment-related mortality characteristics of high-dose chemotherapy (HDC) in patients with relapsed/refractory Ewing sarcoma (ES), osteosarcoma, rhabdomyosarcoma (RMS) and medulloblastoma (MB)., Study Design: Observational study., Place and Duration of Study: Department of Medical Oncology, University of Health Sciences, Gulhane School of Medicine, from January 2016 and April 2020., Methodology: Clinical features and follow-up data of relapsed/refractory ES, osteosarcoma, RMS and MB patients treated with HDC were recorded from the patients' registration database of the hospital. Patients <16 years and those whose medical records were not available were excluded. Progression-free survival (PFS), one-year overall survival (OS) rates and treatment-related mortality (TRM) after the HDC were determined. Ifosfamide, carboplatin and etoposide (HD-ICE) were used as the HDC protocol in all patients., Results: Thirty-seven adult patients were included. PFS was determined as 2.70 ± 0.97 months, 11.57 ± 3.63 months, 3.47 ± 0.44 months and 2.96 ± 0.91 months, for ES, MB, RMS and osteosarcoma, respectively. One-year OS rate was 44.8 ± 14.8% for ES; 75 ± 15.8% for MB. In ES, PFS was found to be better in males than females (p = 0.025). No patient died during HD-ICE. Mortality was observed most frequently in the RMS in the first 100 days (25%)., Conclusion: HD-ICE treatment may be an option in relapsed/refractory small round cell tumours (SRCT). Significant progression-free survival can be achieved in patients who received at least two lines of treatment, with acceptable treatment-related mortality. Key Words: Small round cell tumours, Ewing sarcoma, Osteosarcoma, Rhabdomyosarcoma, Medulloblastoma, High-dose chemotherapy, Autologous stem cell transplantation.

Background: Immunotherapy improves overall survival (OS) in the second and later lines of renal cell carcinoma (RCC) treatment. Recent studies have suggested that antibiotic (ATB) use either shortly before or after the start of immunotherapy could lead to decreased OS. Herein, we evaluate the impact of ATB use on OS in RCC patients treated with nivolumab in a multi-center cohort from Turkey., Methods: The data of 93 metastatic RCC patients treated with nivolumab in the second line or later were retrospectively collected from 6 oncology centers. Previous treatments, sites of metastases, International Metastatic RCC Database Consortium risk classification, and ATB use in the three months before (-3) or three months after (+3) the start of immunotherapy were recorded together with survival data. The association of clinical factors with OS and progression-free survival (PFS) was analyzed with univariate and multivariable analyses., Results: The median age was 61 (interquartile range 54-67), and 76.3% of the patients were male. The median OS of the cohort was 23.75 ± 4.41, and the PFS was 8.44 ± 1.61 months. Thirty-one (33.3%) patients used ATBs in the 3 months before (-3) or 3 months after (+3) nivolumab initiation. In the multivariable analyses, ATB exposure (HR: 2.306, 95% confidence interval [CI]: 1.155-4.601, P = 0.018) and the presence of brain metastases at the baseline (HR: 2.608, 95% CI: 1.200-5.666, P = 0.015) had a statistically significant association with OS, while ATB exposure was the only statistically significant parameter associated with PFS (HR: 2.238, 95% CI: 1.284-3.900, P = 0.004)., Conclusion: In our study, patients with ATB exposure in the 3 months before or 3 months after the start of immunotherapy had shorter OS. Our findings further support meticulous risk-benefit assessments of prescribing ATBs for patients who are either receiving or are expected to receive immunotherapy., (Copyright © 2021. Published by Elsevier Inc.)

Aim: To evaluate the immunogenicity and safety of the CoronaVac vaccine in patients with cancer receiving active systemic therapy. Methods: This multicenter, prospective, observational study was conducted with 47 patients receiving active systemic therapy for cancer. CoronaVac was administered as two doses (3 μg/day) on days 0 and 28. Antibody level higher than 1 IU/ml was defined as 'immunogenicity.' Results: The immunogenicity rate was 63.8% (30/47) in the entire patient group, 59.5% (25/42) in those receiving at least one cytotoxic drug and 100% (five of five) in those receiving monoclonal antibody or immunotherapy alone. Age was an independent predictive factor for immunogenicity (odds ratio: 0.830; p = 0.043). Conclusion: More than half of cancer patients receiving active systemic therapy developed immunogenicity.

Introduction and Aim: To demonstrate the real-life data about patients who underwent AHSCT due to GCT., Methods: Between November 2016 and April 2020, 64 patients who received CE as high-dose chemotherapy for AHSCT in the Gulhane Education and Research Hospital were included in the study. Sixty-one patients received one AHSCT with CE chemotherapy regimen. Survival data and clinical characteristics were evaluated retrospectively., Results: The mean age of the patients were 31.9 ± 9 (min-max:18-55). With a median follow-up of 10.7 ± 8.7 months, the 1-year progression-free survival (PFS) rate was 57.8%, and the 1-year overall survival rate was 77.5%. Median overall survival (OS) and progression-free survival (PFS) times were 21.5 ± 1.8 (95% CI: 14.5-33.4) and 20 ± 2 months, respectively. The response rate was 72%. There were three treatment-related deaths., Conclusion: This sizeable single-centre study shows that patients with relapsed metastatic GCT are curable by CE as high dose chemotherapy plus AHSCT with reliable toxicity even for a single cycle.

Background: More evidence shows that primary surgery for de novo metastatic breast cancer (BC) prolongs overall survival (OS) in selected cases. The aim of this study was to evaluate the role of locoregional treatment (LRT) in BC patients with de novo stage IV bone only metastasis (BOM)., Methods: The prospective, multicenter registry study BOMET MF14-01 was initiated in May 2014. Patients with de novo stage IV BOM BC were divided into two groups: those receiving systemic treatment (ST group) and those receiving LRT (LRT group). Patients who received LRT were further divided into two groups: ST after LRT (LRT + ST group) and ST before LRT (ST + LRT group)., Results: We included 505 patients in this study; 240 (47.5%) patients in the ST group and 265 (52.5%) in the LRT group. One hundred and thirteen patients (26.3%) died in the 34-month median follow-up, 85 (35.4%) in the ST group and 28 (10.5%) in LRT group. Local progression was observed in 39 (16.2%) of the patients in the ST group and 18 (6.7%) in the LRT group (p = 0.001). Hazard of death was 60% lower in the LRT group compared with the ST group (HR 0.40, 95% CI 0.30-0.54, p < 0.0001)., Conclusion: In this prospectively maintained registry study, we found that LRT prolonged survival and decreased locoregional recurrence in the median 3-year follow-up. Timing of primary breast surgery either at diagnosis or after ST provided a survival benefit similar to ST alone in de novo stage IV BOM BC patients., (© 2021. Society of Surgical Oncology.)

The aim of this study is to determine the power of he international prognostic scoring systems (IPS-7 and IPS-3) and to obtain indices by integrating leukocyte lymphocyte ratio (LLR) and prognostic nutritional index (PNI) factors as prognostic indicators in cases with classical Hodgkin lymphoma (cHL). 1012 patients with cHL were evaluated with 2 different IPS-4 scores with four parameters: stage, age, hemoglobin level, and either LLR or PNI. Statistical package SPSS v 22.0 was used. Two different Cox regression models were obtained for OS and PFS. Model 1 showed LLR ≥ 5,8 as the highest risk for OS and anemia as the highest risk for PFS. Model 2 showed PNI ≤ 45,2 as the highest risk for OS and anemia as the highest risk for PFS. IPS-4 scores obtained by integrating either LLR or PNI to IPS-3 integration of a biologic parameter either LLR or PNI need to be determined with clinical risk scoring parameters., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: COVID-19 will continue to disrupt the diagnosis-treatment process of cancer patients. Dr. Abdurrahman Yurtaslan Ankara Oncology Hospital has been considered as a 'non-pandemic' center ('clean') in Ankara, the capital city of Turkey. The other state hospitals that also take care of cancer patients in Ankara were defined as 'pandemic' centers. This study aimed to evaluate hospital admission changes and the precautionary measures in clean and pandemic centers during the pandemic. The effect of these measures and changes on COVID-19 spreading among cancer patients was also evaluated., Methods: The patients admitted to the medical oncology follow-up, new diagnosis, or chemotherapy (CT) outpatient clinics during the first quarter of pandemic period (March 15-June 1, 2020) of each center were determined and compared with the admissions of the same frame of previous year (March 15-June 1, 2019). COVID-19 PCR test results in clean and pandemic centers were compared with each other. Telemedicine was preffered in the clean hospital to keep on follow-up of the cancer patients as 'noninfected'., Results: In the clean hospital, COVID-19-infected patients that needed to be hospitalized were referred to pandemic hospitals. COVID-19 test positivity rate was eight-fold higher for outpatient clinic admissions in pandemic hospitals (p < 0.001). The number of patients admitted new diagnosis outpatient clinics in both clean and pandemic hospitals decreased significantly during the pandemic compared with the previous year., Conclusion: We consider that local strategic modifications and defining 'clean' hospital model during infectious pandemic may contribute to protect and treat cancer patients during pandemic.

Background: This study was designed to estimate economic burden of lung cancer in Turkey from payer perspective based on expert panel opinion on practice patterns in clinical practice., Methods: In this cost of illness study, direct medical cost was calculated based on cost items related to outpatient visits, laboratory and radiological tests, hospitalizations/interventions, drug treatment, adverse events and metastasis. Indirect cost was calculated based on lost productivity due to early retirement, morbidity and premature death resulting from the illness, the value of lost productivity due to time spent by family caregivers and cost of formal caregivers., Results: Cost analysis revealed the total per patient annual direct medical cost for small cell lung cancer to be €8772), for non-small-cell lung cancer to be €10,167. Total annual direct medical cost was €497.9 million, total annual indirect medical cost was €1.1 billion and total economic burden of lung cancer was €1.6 billion. Hospitalization/interventions (41%) and indirect costs (68.6%) were the major cost drivers for total direct costs and the overall economic burden of lung cancer, respectively., Conclusions: Our findings indicate per patient direct medical costs of small cell lung cancer and non-small-cell lung cancer to be substantial and comparable, indicating the substantial economic burden of lung cancer in terms of both direct and indirect costs. Our findings indicate that hospitalization/interventions cost item and indirect costs were the major cost drivers for total direct costs and the overall economic burden of lung cancer, respectively. Our findings emphasize the potential role of improved cancer prevention and early diagnosis strategies, by enabling cost savings related to drug treatment and metastasis management cost items, in sustainability of cancer treatments.

Objective: Cancers have been reported to worsen the clinical course of coronavirus disease 2019 (COVID-19) infection. We aimed to demonstrate the real-life data on health outcomes in COVID-19-infected cancer patients., Materials and Methods: We analyzed the data of 43 COVID-19-infected cancer patients in our COVID-19 clinics between March 25, 2020, and May 9, 2020, retrospectively., Results: We determined that 1051 patients were followed up with COVID-19 infection and 43 (4%) of them were cancer patients. The mean age of the patients was 64.3 ± 12.3 years. Lung cancer is the most common cancer type among the patients (23.2%). Dyspnea (51.2%) was the most common symptom in the first admission. Typical ground-glass consolidation or patchy appearance with peribronchial thickening resembling bronchopneumonia on high-resolution computed tomography (HRCT) was present in 29 (67.4%) patients. COVID-19 was diagnosed in 14 (32.5%) patients based on reverse transcriptase-polymerase chain reaction analysis of nose-throat swab samples without any sign of lung involvement on HRCT. Total mortality of the COVID-19 infection was 46.5% (n = 20). Presence of heart disease (hazard ratio [HR]: 3.5; 95% confidence interval [CI]: 1.29-9.4), previous surgeries to the respiratory system (HR: 6.95; 95% CI: 1.29-27.7), and presence of dyspnea at admission (HR: 4; 95% CI: 1.31-12.3) were statistically significantly associated with death (P = 0.01, 0.02, and 0.01, respectively)., Conclusion: Our practices supported that cancer patients were more affected by COVID-19 disease than the normal population. However, our findings can not be generalized due to being retrospective and single centered study, Also, we did not compare the findings with noncancer patients with COVID19 disease., Competing Interests: None

The aim of this study is to validate the IPS-3 scoring system as a prognostic indicator in 1012 patients with advanced stage classical Hodgkin Lymphoma (cHL) treated by doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD). According to the IPS-3 scoring system only 3.5 % had high risk and 50.8 % had low risk disease disease and 45.8 % of the cases had intermediate risk disease. Each factors of IPS-7 and IPS-3 scoring systems (age, sex, stage hemoglobin, albumin, lymphocyte count and white cell count) were found to be significant for overall survival (OS) and progression free survival (PFS) according to univariate analyses. Two different multivariate Cox analyses were performed for OS and PFS including the IPS-3/ IPS-7 scoring system parameters. Among 7 risk factors of IPS scoring system, gender and albumin were not found as independent risk factors for both OS and PFS according to cox regression model. But all parameters such as age, stage and hemoglobin those included in IPS-3, were found to be independent significant risk factors for both models obtained for OS and PFS. The results of the study shows that the IPS-3 scoring system can be used as a prognostic indicator in ABVD treated patients in every day practice which is more easily calculate according to the IPS-7., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: To investigate the clinical outcomes of patients with hyponatremia who received supportive treatment or tolvaptan plus supportive treatment and the effects of treatment and other variables on overall survival METHODS: This study included oncology patients who were hospitalized at two oncology centers between January 1, 2016 and December 31, 2019 for hyponatremia (sodium levels < 135 mEq/L) and who received tolvaptan plus supportive treatment (n = 22) or supportive treatment only (n = 42)., Results: The median age of all the patients was 59 years (range 26-85) and 64.1% of the patients were male. There was no statistically significant difference between patients in the tolvaptan plus supportive treatment (TpST) group and the supportive treatment only (ST) group in terms of gender and age (p > 0.05). In the TpST group, recovery days of the hyponatremia after treatment and the length of hospital stay was shorter and hyponatremia symptoms and hospital complications were less frequent compared to the ST group (p < 0.05). There was no significant difference between the TpST group and the ST group in terms of overall survival (OS). OS was shorter in men who were non-responders to hyponatremia treatment and had recurrent hyponatremia. Multivariable analysis showed that normal sodium levels after treatment decreased the risk of death., Conclusion: In the treatment of hyponatremia in cancer patients, TpST was found to have more positive effects on blood sodium levels, length of hospital stay, hospital complications, and hyponatremia symptoms compared to ST. A decreased risk of death was observed in patients with normal sodium levels after treatment.

Aim: Selective intraarterial radionuclide therapy (SIRT) with Yttrium-90 (Y-90) resin microspheres has been applied for hepatocellular carcinoma (HCC) lately. The aim of this study is to present our clinical experience of radiomicrosphere therapy in the treatment of unresectable HCC and determine the proper cases who could benefit from this therapy according to response results yielded by initial staging and control imaging modalities., Methods: We administered 43 Y-90 microsphere therapy to 34 patients with unresectable HCC (twice in 9 patients). Patients with histopathologically confirmed HCC having a life expectancy of ≥3 months; Child A-B, Okuda stage 1-2 and BCLC stage A-B-C classifications were included in the study. The patients were divided into two groups: Group A consisted of 29 patients who responded to Y-90 therapy (complete response, partial response and stable disease), Group B 5 of non-responders (progressive disease). Predefined parameters were evaluated for response to SIRT and compared between two groups., Results: We found a significant decrease in platelet and lymphocyte counts one month after therapy (p=0.02, p=0.01, respectively). On control imaging tests performed 3 months later, we observed complete response in 19% (n=6), partial response in 44% (n=15), stable disease in 25% (n=8) and progressive diease in 12% (n=5) of the patients. Mean overall survival (OS) was 19 (median value: 14) months., Conclusions: Y-90 microsphere therapy is a safe and effective treatment option for the patients with unresectable HCC without any serious side effect. Mean tumor dose delivery and lack of bilobar disease seem the best predictors for treatment success., Key Words: Selective intraarterial Radionuclide therapy, Yttrium-90, hepatocellular carcinoma.

Classical Hodgkin lymphoma (cHL) is considered a curable disease; however, in approximately one-third of the responding patients, the disease relapses following completion of therapy. One of the drugs that have been approved for the treatment of relapsed/refractory cHL is nivolumab, an immune check point inhibitor that shows its effects by blocking the programmed death 1 (PD-1) receptor. In this study, we present a retrospective "real-life" analysis of the usage of nivolumab in patients with relapsed/refractory cHL that have joined the named patient program (NPP) for nivolumab, reflecting 4 years of experience in the treatment of relapsed/refractory cHL. We present a retrospective analysis of 87 patients (median age, 30) that participated in the NPP in 24 different centers, who had relapsed/refractory cHL and were consequently treated with nivolumab. The median follow-up was 29 months, and the median number of previous treatments was 5 (2-11). In this study, the best overall response rate was 70% (CR, 36%; PR, 34%). Twenty-eight of the responding patients underwent subsequent stem cell transplantation (SCT). Among 15 patients receiving allogeneic stem cell transplantation, 9 patients underwent transplantation with objective response, of which 8 of them are currently alive with ongoing response. At the time of analysis, 23 patients remained on nivolumab treatment and the rest discontinued therapy. The main reason for discontinuing nivolumab was disease progression (n = 23). The safety profile was acceptable, with only nine patients requiring cessation of nivolumab due to serious adverse events. The 24-month progression-free and overall survival rates were 58.5% (95% CI, 0.47-0.68) and 78.7% (95% CI, 0.68-0.86), respectively. Eighteen patients died during the follow-up and only one of these was regarded to be treatment-related. With its efficacy and its safety profile, PD-1 blockers became an important treatment option in the heavily pretreated cHL patients.

Background: To describe the prognostic value of neutrophil-lymphocyte ratio and its effect on survival in in patients with advanced renal cell carcinoma., Methods: We retrospectively analyzed 331 patients. The cut-off value of neutrophil-lymphocyte ratio was specified as "3" which is mostly close-and also clinically easily applicable-to the median neutrophil-lymphocyte ratio level of our study group. High group is identified as neutrophil-lymphocyte ratio >3 (n = 160) and low group is identified as neutrophil-lymphocyte ratio ≤3 (n = 163)., Results: A total of 331 (with 211 male and 120 female) patients were enrolled to study. The median age of the patients was 58. The International Metastatic RCC Database Consortium risk score is calculated for the 72.8% (n = 241) of the study group and among these patients, favorable, intermediate, and poor risk rates were 22, 45.2, and 32.8%. The total usage of tyrosine kinase inhibitors reached 78% of the patients. The median overall survival was 32 months versus 11 months in the neutrophil-lymphocyte ratio low and high groups, respectively (HR: 0.49 (95% CI 0.37-0.65), p < 0.001)., Conclusion: In conclusion, the pre-treatment value of elevated neutrophil-lymphocyte ratio might be a predictor of poor overall survival in advanced renal cell carcinoma patients.

Introduction and Aim: To investigate the effect of the prognostic nutritional index on treatment response and survival in patients with metastatic renal cell cancer., Methods: We retrospectively analyzed the treatment modalities; the demographic, clinical and pathological features of 396 patients with RCC and prognostic nutritional index. Based on the median value, patients were grouped as having low and high prognostic nutritional index values. Kaplan-Meier method was used for survival analysis, and Cox-regression analysis was used for multivariate analysis., Results: The median overall survival was 39 months (95% CI 26.1-51.8), 28 months (95% CI 17.9-38) and 7 months (95% CI 4.7-9.2) in patients with favorable, intermediate and poor International Metastatic Renal Cell Carcinoma Database Consortium risk group, respectively. The difference between the groups was statistically significant (p < 0001). Overall survival was 11 months (95% CI 7.5-14.5) in the low-prognostic nutritional index (prognostic nutritional index ≤38.5) group, and 41 months (95% CI 30.5-51.4) in the high prognostic nutritional index (prognostic nutritional index >38.5) group (p < 0.001). In Cox regression analysis, Eastern Cooperative Oncology Group performance score (HR: 2.5), time to systemic treatment (HR: 1.7) and prognostic nutritional index (HR: 1.8) were associated with overall survival., Conclusion: In patients with renal cell cancer, prognostic nutritional index is closely related to survival and has prognostic significance.

Purpose: The purpose of this study was to determine whether primary tumor localization may be a risk factor for relapse and survival in seminomatous germ cell tumors (GCT) patients., Methods: In our study, 612 seminomatous GCT patients diagnosed in 22 centers between 01.01.1989 and 03.02.2019 were retrospectively evaluated. Patient interview information, patient files and electronic system data were used for the study., Results: The primary tumor was localized in the right testis in 305 (49.9%) patients and in 307 (50.1%) in the left testis. Mean age of the patients was 36 years (range 16-85±10.4). The median follow-up period was 47 months (1-298). Recurrence was observed in 78 (12.7%) patients and 29 (4.7%) died during the follow-up period. Four-year overall survival (OS) was 95.4% and 4-year progression-free survival (PFS) was 84.5%. The relationship between localization and relapse was significant in 197 patients with stage 2 and stage 3 (p=0.003). In this patient group, 41 (20.8%) relapses were observed. Thirty (73.2%) of the relapses were in the right testis and 11 (26.8%) in the left testis. Four-year OS was 92.1% in patients with right tumor; and 98.7% in patients with left tumor (p=0.007). When 612 patients were evaluated with a mean follow-up of 4 years, there was a 6.6% survival advantage in patients with left testicular tumor and this difference was significant (p=0.007)., Conclusion: Survival rates of patients with primary right testicular localization were worse compared with left testicular localization, and relapse rates were higher in stage 2 and 3 patients with right testicular localization.

Purpose: Testicular cancer is the most commonly diagnosed solid organ malignancy in 15 to 35 year-old men with 1% incidence among all malignancies. Sixty percent of patients with mild and poor-risk factors need additional treatments. Starting in 1980s, high dose chemotherapy regimens (HDCT) that were not applicable before due to hematological toxicity have been brought into use, and survival and cure possibility have increased. To date, no randomized trial has been conducted to demonstrate superiority of high-dose chemotherapy protocols used for autologous stem cell transplantation (ASCT). Our study aims to compare two commonly used HDCT regimens for a long period, with real-life data., Methods: Approval for thiss retrospective study was obtained from the ethics committee of Gülhane Training and Research Hospital. Fifty refractory testicular cancer patients above 18 years were treated with HDCT and ASCT at Gülhane Training and Research Hospital (January 2011-July 2018)., Results: Fifty metastatic, refractory testicular carcinoma patients with a median age of 34 were included in the study. Ninety per cent of the cases had stage III disease at diagnosis. Except for 8 patients (16%) at mild risk group, all the other patients were at high risk. CE was used as salvage treatment for half of the patients and ICE was used for the other half. Four patients responded completely and 30 responded partially to ASCT. Post transplantation median progression-free survival (PFS) was 22 months. Median overall survival (OS) in the general population was 223.4 months (76.1-370.7). Although there was a difference in OS between chemotherapy groups, the difference was not statistically significant. The mean duration of engraftment in patients treated with CE was 11.2 ± 2.3 days, while in patients receiving ICE it was 15.5 ± 2.1 days. This difference between chemotherapy groups was statistically significant (p<0.001).

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. The presence of 4q12amp has been sporadically reported in small tumor specific series but a large-scale analysis is lacking. We assess the pan-cancer landscape of 4q12amp and provide early clinical support for the feasibility of targeting this amplicon., Experimental Design: Tumor specimens from 132,872 patients with advanced cancer were assayed with hybrid capture based comprehensive genomic profiling which assays 186-315 genes for all classes of genomic alterations, including amplifications. Baseline demographic data were abstracted, and presence of 4q12amp was defined as 6 or more copies of KIT/KDR/PDGFRA. Concurrent alterations and treatment outcomes with matched therapies were explored in a subset of cases., Results: Overall 0.65% of cases harbored 4q12amp at a median copy number of 10 (range 6-344). Among cancers with >100 cases in this series, glioblastomas, angiosarcomas, and osteosarcomas were enriched for 4q12amp at 4.7%, 4.8%, and 6.4%, respectively (all p < 0.001), giving an overall sarcoma (n = 6,885) incidence of 1.9%. Among 99 pulmonary adenocarcinoma cases harboring 4q12amp, 50 (50%) lacked any other known driver of NSLCC. Four index cases plus a previously reported case on treatment with empirical TKIs monotherapy had stable disease on average exceeding 20 months., Conclusion: We define 4q12amp as a significant event across the pan-cancer landscape, comparable to known pan-cancer targets such as NTRK and microsatellite instability, with notable enrichment in several cancers such as osteosarcoma where standard treatment is limited. The responses to available TKIs observed in index cases strongly suggest 4q12amp is a druggable oncogenic target across cancers that warrants a focused drug development strategy., Implications for Practice: Coamplification of the receptor tyrosine kinases (rtks) KIT/KDR/PDGFRA (4q12amp) is present broadly across cancers (0.65%), with enrichment in osteosarcoma and gliomas. Evidence for this amplicon having an oncogenic role is the mutual exclusivity of 4q12amp to other known drivers in 50% of pulmonary adenocarcinoma cases. Furthermore, preliminary clinical evidence for driver status comes from four index cases of patients empirically treated with commercially available tyrosine kinase inhibitors with activity against KIT/KDR/PDGFRA who had stable disease for 20 months on average. The sum of these lines of evidence suggests further clinical and preclinical investigation of 4q12amp is warranted as the possible basis for a pan-cancer drug development strategy., (© 2019 The Authors. The Oncologist published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)