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    A New Mortality Prediction Model in Advanced Stage Cancer Patients Requiring Hospitalisation while Receiving Active Systemic Therapy
    (Coll Physicians & Surgeons Pakistan, 2023) Karaboyun, Kubilay; Iriagac, Yakup; Cavdar, Eyyup; Avci, Okan; Seber, Erdogan Selcuk
    Objective: To predict short and long-term mortality in patients who were admitted to the emergency department and then hospitalised unplanned in medical oncology-ward.Study Design: An observational study.Place and Duration of the Study: Department of Medical Oncology, Tekirdag Namik Kemal University Hospital, Tekirdag, Turkiye, from May 2021 to May 2022.Methodology: Consecutive patients admitted to the emergency department with unplanned hospitalisation in the oncology ward, were included. Patients receiving treatment with the curative intent, patients hospitalised for febrile neutropenia, and terminally ill patients requiring intensive care unit follow-up at admission were excluded from the study. Univariate and multivariate logistic regression analyses were used to identify predictive factors for short and long-term mortality-dependent variables.Results: This study included 253 advanced cancer patients. The number of patients who died in the ward within 10 days (short-term mortality) was 28 (11.1%). Ninety patients (35.6%) died afterwards anytime in the ward during the study (long-term mortality). In the multi-variate analysis established for short-term mortality, higher ALT (OR = 6.75, 95% CI: 2.09 -21.85, p=0.001), rapid deterioration in perfor-mance status (OR = 5.49, 95% CI: 1.81-16.67, p=0.003), higher CRP (OR = 5.86, 95% CI: 1.20-28.53, p=0.029), higher procalcitonin (OR = 7.94, 95% CI: 0.99 -63.82, p=0.051), and higher lactate (OR = 2.47, 95% CI: 0.94-6.51, p=0.067) showed significant predictive features.Conclusion: The decision of whether to continue treatment or not is challenging in cancer patients who require unplanned hospitalisation while receiving palliative systemic therapy. New mortality estimation models can be used in making the transition from life-long to pallia-tive treatments.
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    A Novel Prognostic Indicator for Immunotherapy Response: Lymphocyte-to-Albumin (LA) Ratio Predicts Survival in Metastatic NSCLC Patients
    (Mdpi, 2024) Yildirim, Sedat; Dogan, Akif; Akdag, Goncagul; Cavdar, Eyyup; Kinikoglu, Oguzcan; Oksuz, Sila; Yildiz, Hacer Sahika
    Objective: Immunotherapies are commonly employed for the treatment of non-small-cell lung cancer (NSCLC). However, predictive biomarkers still need to be improved to predict responses to these agents. The lymphocyte-albumin (LA) laboratory index has not been evaluated before in this patient group. The aim of this study was to analyze the relation between the LA index and the survival rate of metastatic NSCLC patients who had immunotherapy after at least one round of chemotherapy. Methods: The research included 227 patients diagnosed with metastatic NSCLC, who were administered nivolumab after at least one round of chemotherapy. The LA index was calculated by multiplying lymphocyte count and albumin concentration. The optimal threshold values for the index were established by the examination of the ROC curve for both overall survival (OS) and progression-free survival (PFS). Oncological data were obtained retrospectively from patient files, and survival analyses were performed. Results: The median follow-up was 7.9 months. Progression was observed in 129 (56.9%) patients. A total of 97 (42.7%) patients died during the follow-up. The cutoff values of the LA index to predict OS and PFS were determined as 52.87 and 57.67, respectively. The low-LA group had significantly lowered OS and PFS compared to the high-LA group. LA was found to be an independent prognostic factor for PFS (hazard ratio 4.47; 95% confidence interval, 2.73-7.34; p < 0.001) and OS (hazard ratio 6.24; 95% confidence interval, 3.46-11.25; p < 0.001) in the multivariate regression analysis. Conclusions: In this study, we observed that the LA index independently predicts OS and PFS in immunotherapy-treated metastatic NSCLC patients. Its ease of application, low cost, and noninvasive nature make it a potential guide for clinicians in predicting treatment responses and survival.
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    Comparison of three equations for estimating glomerular filtration rate as predictors of cisplatin-related acute kidney injury in lung cancer patients with normal renal function
    (Wolters Kluwer Medknow Publications, 2024) Karaboyun, Kubilay; Iriagac, Yakup; Cavdar, Eyyup; Avci, Okan; Seber, Erdogan S.
    Objective: Cisplatin-associated acute kidney injury is a common clinical event that causes increased morbidity and mortality in cancer patients even if they are categorized as having normal functioning kidneys. We aimed to determine predictive factors that can predict acute kidney injury associated with cisplatin therapy in patients with normal renal function by comparison of pre-chemotherapy estimated glomerular filtration rates calculated separately by Cockcroft and Gault (CG), the Modification of Diet in Renal Disease (MDRD), and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EP & Idot;) equations and accompanying patient-associated factors. Materials and Methods: A total of 200 patients diagnosed with lung cancer and determined to have normal functioning kidneys and considered cisplatin eligible by the attending physician before chemotherapy were included in this retrospective study. Acute kidney injury after cisplatin chemotherapy (c-AKI) was determined according to the National Cancer Institute's Common Terminology Criteria for Adverse Events v4.03. Pre-chemotherapy serum laboratory parameters and clinico-histopathological characteristics of patients were recorded from the hospital electronic system. The optimal cut-off for eGFR methods was determined by the area under the receiver operating characteristic curve (ROC-AUC) analysis. Predictive factor analysis for c-AKI was performed by regression analyses. Results: C-AKI developed in 39 (19.5%) patients. In the univariate analysis, a significant correlation was observed between c-AKI and high body mass index (BMI) before treatment, older age (>62.5), female gender, eGFR by MDRD (<= 94.5 mL/min) and eGFR by CKD-EPI (<= 91.5 mL/min). There was no relation between eGFR by CG and c-AKI. Two different multivariate models were established. Model 1 showed that female gender (odds ratio [OR] =4.90, 95% confidence interval [CI]: 1.52-15.79, P = 0.008) and eGFR by MDRD less than or equal to 94.5 mL/min (OR = 3.52, 95% CI: 1.68-7.38, P = 0.001) were predictive markers for c-AKI. In Multivariate Model 2, female gender (OR = 5.51, 95% CI: 1.70-17.83, P = 0.004) and eGFR by CKD-EPI less than or equal to 91.5 mL/min (OR = 3.52, 95% CI: 1.67-7.42, P = 0.001) were found to be predictive markers for c-AKI. Conclusions: This study revealed that eGFR calculated based on MDRD (<= 94.5 mL/min/m2) or CKD-EPI (<= 91.5 mL/min/m2) before chemotherapy indicates a strong tendency for c-AKI. In addition, we detected a high risk of c-AKI for females compared to their counterparts. Although eGFR 60 mL/min is considered the threshold level to accept patients as cisplatin-eligible, we recommend close follow-up of high-risk patients for cisplatin nephrotoxicity we detected in our models.
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    Creatine Kinase (CK)-MB and CK-MB-to-Total-CK Ratio: A Novel Predictive Marker for Pathologic Complete Response in Breast Cancer Treated with Neoadjuvant Chemotherapy
    (Akad Doktorlar Yayinevi, 2024) Cavdar, Eyyup; Karaboyun, Kubilay; Iriagac, Yakup; Celikkol, Aliye; Elcicek, Omer; Avci, Okan; Seber, Erdogan
    Breast cancer is the most common cancer and neoadjuvant chemotherapy(NAC) is one of the important treatment modalities in early stage breast cancer. The aim of this study was to investi-gate the ability of serum CK-MB and CK-MB/CK to be an ideal predictive marker for pathologic complete response (pCR) in breast cancer patients receiving NAC and to determine its rela-tionship with clinicopathologic factors. A total of 135 breast cancer patients receiving NAC were included in this retrospective study. The pre-NAC serum laboratory values and clinicopathologi-cal features of the patients were recorded. Regression analysis was used to do predictive factor analysis for pCR. In the statistical analysis, serum CK-MB level was associated with axillary status, PgR status, ER status, and HER2 status. A significant relationship between CK-MB/CK and axillary status and histological grade was found. PgR negativity, ER negativity, high histo-logical grade, axillary negativity, NLR, CK-MB elevation, and high CK-MB/CK ratio were found to be predictive factors for pCR in the univariate regression analysis.CK-MB (OR= 3.48, p= 0.032) and CK-MB/CK ratio (OR= 3.16, p= 0.028) were revealed to be strong predictors of pCR in established multivariate models.In survival analysis, recurrence-free survival (RFS) were shorter in patients with low CK-MB/CK ratio (p= 0.045). There was no significant relationship between CK-MB level and RFS (p= 0.315). In summary, in breast cancer patients who have re-ceived NAC, serum CK-MB level and CK-MB/CK ratio are independent predictors of pCR.To the best of our knowledge, this study is the first to assess these variables' predictive impact on NAC response in breast cancer patients.
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    Decrease in estimated glomerular filtration rates in non-small cell lung cancer patients treated with crizotinib
    (Wolters Kluwer Medknow Publications, 2023) Iriagac, Yakup; Cavdar, Eyyup; Karaboyun, Kubilay; Tacar, Seher Yildiz; Mustafayev, Fatma Nihan Akkoc; Celik, Emir; Avci, Okan
    Introduction: Crizotinib is a tyrosine kinase inhibitor used in patients with non-small cell lung cancer, and there are uncertainties about its effect on kidney function. In this study, it was aimed to document the possible adverse effect of the drug on kidney functions. Materials and Methods: The estimated glomerular filtration rates (eGFRs) of the patients were calculated by creatinine-based Chronic Kidney Disease Epidemiology Collaboration and compared by months using the paired samples t-test. Kaplan-Meier survival method was used for progression-free survival and overall survival (OS) analysis. Results: Twenty-six patients who received crizotinib were included in the study, and the median progression-free survival time with crizotinib was 14.2 months and the median OS time was 27.4 months. There was a significant reduction of eGFR after the 1(st) month of crizotinib treatment when compared to the rate before treatment initiation (P < 0.001). The eGFR values at the end of the 1(st) month and the 2(nd) month of treatment and the 2(nd) and 3(rd) months of treatment were statistically similar (P = 0.086, P = 0.663; respectively). This decrease in eGFR values was reversible, and there was no difference detected between pretreatment and posttreatment discontinuation (P = 0.100). Conclusion: A reversible decrease in renal functions was detected in patients using crizotinib. When the literature data are examined, it is thought that the reason for this decrease may be related to the increase in renal inflammation or a pseudo decrease due to the decrease in creatinine excretion. When evaluating renal functions in these patients, using noncreatine-based (iothalamate, etc.) calculations can give more accurate results.
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    Efficacy of Neoadjuvant Chemotherapy in Lobular and Rare Subtypes of Breast Cancer
    (Coll Physicians & Surgeons Pakistan, 2024) Seber, Erdogan Selcuk; Iriagac, Yakup; Cavdar, Eyyup; Karaboyun, Kubilay; Avci, Okan; Yolcu, Ahmet; Gurdal, Sibel Ozkan
    Objective: To determine the predictive factors for the pathological complete response (pCR) in patients with non-ductal invasive breast cancer (ND-BC) receiving neoadjuvant chemotherapy.Study Design: Observational study.Place and Duration of the Study: Departments of Medical Oncology, Tekirdag Namik Kemal University, Sirnak State Hospital, Aydin Adnan Menderes University, Marmara University, Bakirkoy Sadi Konuk Hospital, Basaksehir Cam and Sakura Hospital, Sakarya University, Balikesir Ataturk Hospital, Turkiye, from April 2016 to December 2022.Methodology: A total of 222 non-metastatic breast cancer patients who received neoadjuvant chemotherapy were included in this retrospective multicentric study. The clinicopathologic data were obtained from the hospitals' electronic-record-system. The logistic regression models were used to identify predictive factors for pCR.Results: One hundred and twenty-six patients (56.8%) had invasive lobular carcinoma and 28 patients (12.6%) had signet ring cell/mucinous carcinoma. A total of 45 patients (20.3%) achieved pCR. The pCR rate was 14.3% for lobular carcinoma and 17.9% for signet ring cell/mucinous carcinoma. The univariate analysis showed that estrogen receptor-negative tumours (p = 0.017), high Ki-67 (p = 0.008), high histologic grade (p<0.001), HER2+ expression (p<0.001), and non-lobular histologic type (p = 0.012) were predictive factors for pCR. The multivariate model revealed that HER2 expression (p<0.001) and Ki-67 (p = 0.005) were independent predictors.Conclusion: Neoadjuvant chemotherapy demonstrated effectiveness in ND-BC patients, leading to favourable pCR rates and enabling breast-conserving surgery. Predictive markers for pCR varied depending on histologic types, with HER2 expression, ER status, Ki-67, and histologic grade showing significance in non-ductal subtypes, while HER2 status alone was predictive in lobular carcinoma.
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    Fertility Desire and Protection Practices Among Turkish Young Breast Cancer Patients Treated with Chemotherapy
    (2024) Karaoyun, Kubilay; Cavdar, Eyyup; İriağaç, Yakup; Tacar, Seher Yıldız; Avcı, Okan; Seber, Selçuk
    Objectives: This study aims to reflect the oncofertility practice in Turkey as a developing country, by investigating young breast cancer patients' fertilization preservation attitudes and their post-treatment fertility status. Methods: Young breast cancer patients(<42 years) examined for breast cancer follow-up at the medical oncology out- patient clinic were consecutively included in the study. Patients with metastatic, infertile, or no menstrual cycle at the time of diagnosis and women who were less than 3 years from their last chemotherapy cycle were excluded. A ques- tionnaire on the desire for childbearing in the future, the fertility preservation preferences at the time of diagnosis, reproductive history was surveyed with patients. Results: 123 patients were enrolled in the study. 23.5% of the patients reported that they had a desire to give birth in the future at the time of diagnosis. For fertility preservation; 6 patients used embryo or oocyte cryopreservation, and 16 patients used LHRHa during chemotherapy. Nulliparous patients were more likely than others who had at least one child to pursue fertility preservation (p=0.001) and to be interested in having children in the future (p<0.001). Conclusion: This study revealed that oncofertility practices should be encouraged to improve the quality of life of sur- vivors along with cancer treatment in developing countries. Even with fertility preservation, the chances of a successful pregnancy are significantly low. Physicians should offer protection options to all patients regardless of their previous childbearing status, and fertilization counseling should also be discussed during all the post-treatment visits as well as pre-treatment settings.
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    Is the serum level of survivin, an antiapoptotic protein, a potential predictive and prognostic biomarker in metastatic pancreatic cancer?
    (Lippincott Williams & Wilkins, 2023) Demirci, Nebi Serkan; Cavdar, Eyyup; Erdem, Gokmen Umut; Hatipoglu, Engin; Celik, Emir; Sezer, Sevilay; Yolcu, Ahmet
    In the present study, we aimed to assess the association between the serum survivin level and overall survival and treatment response rates in metastatic pancreatic cancer (MPC). Serum samples were prospectively collected from 41 patients with newly diagnosed MPC patients and 41 healthy individuals (control group) to assess the survivin levels. The median survivin level was 136.2ng/mL in patients with MPC and 52ng/mL in healthy individuals (P = .028). Patients were divided into low- and high-survivin groups according to the baseline median survivin level. Patients with a high serum survivin level compared with a low serum survivin level had shorter median progression-free survival (2.39 vs 7.06 months; P = .008, respectively) and overall survival (3.74 vs 9.52 months; P = .026, respectively). Patients with higher serum survivin levels had significantly worse response rates (P = .007). The baseline high level of serum survivin in patients with MPC may be associated with treatment resistance and poor prognosis. A confirmation will be needed for these results in future large multicenter prospective studies.
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    Potential drug-drug interactions in outpatient lung cancer patients in a university hospital
    (Karger, 2024) Demirkapu, Mahluga Jafarova; Cavdar, Eyyup
    Introduction: Concomitant use of drugs in the same or different indications can sometimes lead to undesirable interactions. The prevalence of drug interactions is high in cancer patients. In this study, we aimed to determine the frequency and clinical severity of drug interactions in outpatient lung cancer patients. Methods: The drugs used, kidney and liver blood analysis results of 160 outpatient lung cancer patients over the age of 18 who received chemotherapy between October 2020 and July 2021 were evaluated. The Lexi-Interact online database was used to identify the types of clinically significant drug interactions, frequently interacting drugs, and clinical outcomes predicted by the databases. Results: The average number of drugs per patient was 4.2 +/- 2.3. It was determined that there was a relationship between multi-drug use and comorbidity, and the number of drugs used increased as the number of diagnoses increased. A relationship was also found between potential drug-drug interactions (pDDI), which we observed in 52.5% of the patients, and the number of drugs used and age. The most common clinically significant C (36.9%), D (16.9%) and X (10.6%) type pDDI were detected between conventional paclitaxel-hydrochlorothiazide, conventional paclitaxel-carboplatin, and ipratropium-tiotropium, respectively. Conclusions: The use of frequently interacting drugs in outpatient lung cancer patients can lead to pDDI. In these patients, the application of therapy by observing the drug-drug interaction may improve the quality of life.
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    Tamoxifen or aromatase inhibitors: which one is the culprit of urinary incontinence in premenopausal breast cancer patients receiving adjuvant hormone therapy?
    (Springer, 2023) Karaboyun, Kubilay; Cavdar, Eyyup; Iriagac, Yakup; Celebi, Abdussamet; Kapagan, Tanju; Gulturk, Ilkay; Demir, Ozden
    AimThe primary aim of this study was to compare tamoxifen versus aromatase inhibitors (AI) in terms of urinary incontinence (UI) in premenopausal female patients receiving adjuvant hormone therapy for breast cancer. A secondary aim was to investigate the prevalence and the affecting factors of UI.MethodsThis study was designed as a multicenter, cross-sectional that included consecutive premenopausal breast cancer patients <= 50 years of age receiving tamoxifen (with/without LHRHa) or AI (with LHRHa) for at least 6 months, between June 2021 and September 2022. Patients with urinary incontinence before hormone treatments and metastatic patients were excluded from the study. Turkish validation of The International Consultation on Incontinence Modular Questionnaire Urinary Incontinence Short Form (ICIQ UI-SF) was used to determine the UI. Using logistic regression methods, we analyzed potential predictive factors for UI.ResultsA total of 206 breast cancer patients were included in this study. A total of 120 (58.2%) patients were receiving tamoxifen plus LHRHa, 40 (19.4%) patients were receiving aromatase inhibitor plus LHRHa, and 46 (22.3%) patients were receiving tamoxifen only. In this study, the prevalence of urinary incontinence was found to be 35.9% (n:74). 41% of the patients receiving tamoxifen and 15.0% of those receiving aromatase inhibitors had complaints of urinary incontinence. There was a statistically significant difference between patients receiving tamoxifen or aromatase inhibitor in terms of urinary incontinence (p=0.001). In the univariate analysis established to predict UI, parity (>= 2 vs <2) (OR = 3.23, 95% CI: 1.62-6.46, p= 0.001), tamoxifen (vs AI) (OR = 3.97, 95% CI: 1.58-9.98, p= 0.003), age ( >= 40 vs. <40) (OR = 2.80, 95% CI: 1.37-5.71, p= 0.005), vaginal deliveries (>= 2 vs. <2) (OR = 3.28, 95% CI: 1.44-7.46, p= 0.005), hypertension (OR = 3.59, 95% CI: 1.43-9.02, p= 0.007), diuretic use (OR = 2.55, 95% CI: 1.09-5.95, p= 0.031) ), and body mass index (>= 25 vs <25) (OR = 1.94, 95% CI: 1.05-3.63), p= 0.034) was found to be predictive. Tamoxifen (OR = 4.71, 95% CI: 1.77-12.56, p= 0.002), hypertension (OR = 3.48, 95% CI: 1.27-9.52, p= 0.015), and age (OR = 2.35, 95% CI: 1.10-5.02, p= 0.027) remained independent predictors for incontinence in multivariate analyses.ConclusionWe found that tamoxifen had increased the risk of urinary incontinence compared to aromatase inhibitors in patients receiving hormone therapy for breast cancer. In addition, we showed that age and hypertension were also independent predictors for UI. In the context of quality of life, we recommend close follow-up of these patients, as drug adherence may be affected in the event of urinary incontinence.
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    The Role of Interleukin-20 in Paclitaxel-Associated Peripheral Neuropathy in Non-Metastatic Breast Cancer Patients Receiving Chemotherapy
    (Galenos Publ House, 2023) Karaboyun, Kubilay; Cavdar, Eyyup; Iriagac, Yakup; Yilmaz, Ahsen; Celikkol, Aliye; Avci, Okan; Seber, Erdogan Selcuk
    Introduction: This study investigated the relationship between serum interleukin-20 (IL-20) levels and paclitaxel-associated neuropathy in patients with non-metastatic breast cancer. Paclitaxel-induced peripheral neuropathy (PIPN) is a significant side effect of paclitaxel chemotherapy, and the exact mechanism underlying PIPN is not fully understood. Methods: This prospective observational study was conducted with non-metastatic breast cancer patients between January 2022 and November 2022. Neuropathy symptoms were evaluated using the QLQ-CIPN20 questionnaire, and serum IL-20 levels were measured at three time points: before chemotherapy, on the 7(th) day after the first paclitaxel treatment, and after the last treatment. Univariate and multivariate logistic regression analyses were performed to identify factors predicting PIPN. Results: This study was completed with 59 female patients. During the study, 47 patients (79.6%) reported any degree of neuropathy, whereas 12 patients (20.4%) had no neuropathy. Univariate analysis to predict neuropathy measured on day 7 after first paclitaxel administration demonstrated that age, body mass index, 7(th)-day serum IL-20 level, and last cycle serum IL-20 level were predictive for PIPN. Conclusion: This study demonstrated the relationship between serum IL-20 levels and paclitaxel-related neuropathy in breast cancer patients. Further research targeting the function of IL-20 is needed to investigate potential strategies to prevent and treat PIPN.