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90 day and 1-year mortality and renal outcomes of patients who started hemodialysis treatment for the first time
(Asoc Regional Dialisis Trasplantes Renales, 2023) Karaboyun, Kubilay; Girgin, Sinem; Yilmaz, Murvet
Aim: This study aims to investigate the 90-day and 1-year mortality and the affecting factors of mortality in patients who have started dialysis treatment for the first time.Methods: Patients who started intermittent hemodialysis for the first time in the hemodialysis unit were evaluated. Patients who received hemodialysis treatment for any reason before, patients who underwent hemodialysis due to methyl alcohol, lithium, or mushroom poisoning, and patients who started dialysis in the intensive care unit were excluded from the study. The clinical and laboratory data were obtained from the patients, at admission time, from the electronic data record system and patients' charts. Univariate and multivariate logistic regression analyses were used to identify predictive factors for 90-days and 1-year mortality-dependent variables.Results: 229 patients were included in this study. 133(58.8%) of the patients were male, 96(41.9%) were female, and the median age was 64 years. While 166 patients had pre-existing renal disease, 63 patients had no prior renal disease. The number of patients who died within 90 days, which refers to short-term mortality, was 49 (21.4%). 73 patients (31.9%) died in one year (long-term mortality). At the end of one year, 38% of the whole group of patients continued receiving renal replacement therapy, while 10% of all CKD patients had not a requirement of dialysis, and only 9.17% of the patients had renal recovery.In the multivariate analysis established for short-term mortality, the following parameters showed significant predictive features: ejection fraction (OR = 3.80, 95% CI: 1.05-13.72, p=0.042), CRP (OR = 0.20, 95% CI: 0.04-0.92, p= 0.039), age (OR = 0.21, 95% CI: 0.05-0.91, p= 0.038), and diastolic blood pressure (OR = 0.08, 95% CI: 0.02-0.28, p< 0.001). The multivariate analysis for long-term mortality indicated that systolic blood pressure (OR = 0.26, 95% CI: 0.08-0.82, p= 0.022), diastolic blood pressure (OR = 0.21, 95% CI: 0.68-0.66, p= 0.008), and potassium (OR = 0.27, 95% CI: 0.10-0.70, p= 0.007) were independent predictive markers.Conclusion: Patients with CKD who have not yet started hemodialysis treatment should be followed closely, as hypervolemia, hypotension, and hemodynamic instability increase the risk of death, according to our study. In addition, we recommend that clinical conditions such as hemodynamic instability or sepsis, which may cause hypotension in AKI-D, should be addressed as soon as possible, and optimizing the fluid-electrolyte balance carefully in those patients we determined to be at risk.
A logarithmic model for hormone receptor-positive and breast cancer patients treated with neoadjuvant chemotherapy
(Assoc Medica Brasileira, 2023) Seber, Erdoğan Selçuk; İriağaç, Yakup; Çavdar, Eyyüp; Karaboyun, Kubilay; Avcı, Okan; Yolcu, Ahmet; Gürdal, Sibel Özkan; Öznur, Meltem
OBJECTIVE: The aim of this study was to investigate the predictive importance of the previously validated log(ER)*log(PgR)/Ki-67 predictive model in a larger patient population.METHODS: Patients with hormone receptor positive/HER-2 negative and clinical node positive before chemotherapy were included. Log(ER)*log(PgR)/ Ki-67 values of the patients were determined, and the ideal cutoff value was calculated using a receiver operating characteristic curve analysis. It was analyzed with a logistic regression model along with other clinical and pathological characteristics.RESULTS: A total of 181 patients were included in the study. The ideal cutoff value for pathological response was 0.12 (area under the curve=0.585, p=0.032). In the univariate analysis, no statistical correlation was observed between luminal subtype (p=0.294), histological type (p=0.238), clinical t-stage (p=0.927), progesterone receptor level (p=0.261), Ki-67 cutoff value (p=0.425), and pathological complete response. There was a positive relationship between numerical increase in age and residual disease. As the grade of the patients increased, the probability of residual disease decreased. Patients with log(ER)*log(PgR)/Ki-67 above 0.12 had an approximately threefold increased risk of residual disease when compared to patients with 0.12 and below (odds ratio: 3.17, 95% confidence interval: 1.48-6.75, p=0.003). When age, grade, and logarithmic formula were assessed together, the logarithmic formula maintained its statistical significance (odds ratio: 2.47, 95% confidence interval: 1.07-5.69, p=0.034).CONCLUSION: In hormone receptor-positive breast cancer patients receiving neoadjuvant chemotherapy, the logarithmic model has been shown in a larger patient population to be an inexpensive, easy, and rapidly applicable predictive marker that can be used to predict response.
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.
A new predictive marker for predicting response after neoadjuvant chemotherapy in hormone receptor positive/HER2-negative patients: a logarithmic model
(Zerbinis Publications, 2021) İriağaç, Yakup; Çavdar, Eyyüp; Karaboyun, Kubilay; Tacar, Seher Yıldız; Taskaynatan, H.; Avcı, Okan; Seber, Erdoğan Selcuk; Yolcu, A.; Gürdal, Sibel Özkan; Öznur, M.; Seber, E.S.
Purpose: Estrogen receptor (ER) and progesterone receptor (PgR) levels as well as Ki-67 expression levels are independent predictive markers in patients with hormone receptor-positive breast cancer. In this study, we investigated the predictive significance of the formula of log (ER)*log (PgR)/Ki-67, which was created using 3 independent predictive markers, for the pathological complete response of the Hormone Receptor (HR)-positive/HER2-negative breast cancer patients receiving neoadjuvant chemotherapy (NACT). Methods: This retrospective study included 126 patients with HR-positive/HER2-negative breast cancer and axillary lymph node metastasis who received NACT. The log (ER)*log (PgR)/Ki-67 value was calculated from the pre-NACT pathological evaluation results in all patients. We determined the ideal predictive cut-off value, which separates patients into 2 groups according to pathological complete response (pCR) and pathological non-complete response (non-pCR), using Receiver Operating Characteristic (ROC) curve analysis. According to this cut-off point, patients were divided into 2 groups as cut-off ratio high and cut-off ratio low and were compared using logistic regression analysis along with clinicopathological features. Results: According to the predictive model, we estimated the ideal cut-off value that distinguishes patients as pCR and non-pCR to be 0.12 (p=0.015). According to this cut off value, %54.8 of the patients were categorized as cut-off value high and %46.2 were cut-off value low. The non-pCR rates of the groups were 91.3% and %71.9, respectively(p=0.004). A cutoff value of 0.12 provided the feature of being a predictive marker in the univariate analysis for distinguishing between pCR and non-pCR (OR=4.09 95% CI 1.48-11.33, p=0.007), and it preserved this feature in the multivariate analysis. (OR=3.27, 95% CI 1.12-9.56, p=0.030). Conclusion: The formula of log (ER)*log (PgR)/Ki-67 can be used as a simple and easy-to-use predictive marker for response to neoadjuvant therapy in patients with HR-positive/HER2-negative breast cancer receiving NACT. © 2021 Zerbinis Publications. All rights reserved.
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.
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.
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.
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.
Efficacy of subsequent treatments in patients with hormone-positive advanced breast cancer who had disease progression under CDK 4/6 inhibitor therapy
(BioMed Central Ltd, 2023) Karaçın, Cengiz; Öksüzoğlu, Berna; Demirci, Ayşe; Keskinkılıç, Merve; Baytemur, Naziyet Köse; Yılmaz, Funda; Selvi, Oğuzhan; Karaboyun, Kubilay
Background: There is no standard treatment recommended at category 1 level in international guidelines for subsequent therapy after cyclin-dependent kinase 4/6 inhibitor (CDK4/6) based therapy. We aimed to evaluate which subsequent treatment oncologists prefer in patients with disease progression under CDKi. In addition, we aimed to show the effectiveness of systemic treatments after CDKi and whether there is a survival difference between hormonal treatments (monotherapy vs. mTOR-based). Methods: A total of 609 patients from 53 centers were included in the study. Progression-free-survivals (PFS) of subsequent treatments (chemotherapy (CT, n:434) or endocrine therapy (ET, n:175)) after CDKi were calculated. Patients were evaluated in three groups as those who received CDKi in first-line (group A, n:202), second-line (group B, n: 153) and ? 3rd-line (group C, n: 254). PFS was compared according to the use of ET and CT. In addition, ET was compared as monotherapy versus everolimus-based combination therapy. Results: The median duration of CDKi in the ET arms of Group A, B, and C was 17.0, 11.0, and 8.5 months in respectively; it was 9.0, 7.0, and 5.0 months in the CT arm. Median PFS after CDKi was 9.5 (5.0–14.0) months in the ET arm of group A, and 5.3 (3.9–6.8) months in the CT arm (p = 0.073). It was 6.7 (5.8–7.7) months in the ET arm of group B, and 5.7 (4.6–6.7) months in the CT arm (p = 0.311). It was 5.3 (2.5–8.0) months in the ET arm of group C and 4.0 (3.5–4.6) months in the CT arm (p = 0.434). Patients who received ET after CDKi were compared as those who received everolimus-based combination therapy versus those who received monotherapy ET: the median PFS in group A, B, and C was 11.0 vs. 5.9 (p = 0.047), 6.7 vs. 5.0 (p = 0.164), 6.7 vs. 3.9 (p = 0.763) months. Conclusion: Physicians preferred CT rather than ET in patients with early progression under CDKi. It has been shown that subsequent ET after CDKi can be as effective as CT. It was also observed that better PFS could be achieved with the subsequent everolimus-based treatments after first-line CDKi compared to monotherapy ET. © 2023, The Author(s).
Efficacy of subsequent treatments in patients with hormone-positive advanced breast cancer who had disease progression under CDK 4/6 inhibitor therapy (vol 23, 136, 2023) [correction]
(Bmc, 2023) Karaçın, Cengiz; Öksüzoğlu, Berna; Demirci, Ayşe; Keskinkılıç, Merve; Baytemur, Naziyet Köse; Yılmaz, Funda; Selvi, Oğuzhan; Karaboyun, Kubilay
[Abstract Not Available]
Evaluating inflammatory markers as predictive tools for advanced non-small cell lung cancer receiving nivolumab Predictive markers for nivolumab response in advanced NSCLC
(Bayrakol Medical Publisher, 2023) Karaboyun, Kubilay
Aim: Non-small cell lung cancer (NSCLC) is a significant cause of cancer-related morbidity and mortality worldwide. In recent years, immunotherapies such as Nivolumab have revolutionized treatment strategies, demonstrating enhanced survival and response profiles compared to traditional platinum-based therapies. This study elucidated the prognostic significance of pretreatment hematological parameters, including Neutrophil-Lymphocyte Ratio (NLR), Systemic Immune-Inflammation Index (SII), and Prognostic Nutritional Index (PNI), in NSCLC patients undergoing Nivolumab treatment. Material and Methods: This retrospective study included patients treated with Nivolumab for pathologically proven advanced NSCLC between January 2019 and March 2021. Hemogram parameters and clinicopathological and clinicopathological factors before Nivolumab treatment were recorded from the hospital's electronic data record system. Survival analysis was conducted using the Kaplan-Meier method and the Log-Rank test was utilized for comparison. Multivariate analysis of factors affecting survival was performed with the Cox proportional-hazards model. Results: Ninety-two patients were included in this study. The median OS and PFS for all patients included in the analysis were 14.5 months and 11.1 months, respectively. The ideal cut-off value dividing NLR into 2 for overall survival time was calculated as 1.89 (AUC: 0.694, p=0.002) using Roc-Curve. In univariate analysis, ECOG performance score (p<0.001), leukocytes (p < 0.029), high neutrophil (p < 0.018) as well as NLR (p <0.018) were found to be associated with worse overall survival. Multivariate Cox regression model demonstrated that ECOG (HR=3.54, 95% CI, 1.46-8.60, p =0.005) and NLR (HR=1.52, CI 1.16 - 2.01, p=.003) were significant predictors factors for survival. Discussion: These results underline the critical role of inflammation and immune response in tumor progression and therapeutic outcomes. The identified markers offer a practical means of predicting patient responses to Nivolumab therapy, aiding in personalized treatment decisions. As NSCLC treatment paradigms shift towards immunotherapy, these easily accessible parameters could aid clinicians in selecting optimal therapeutic strategies for individual patients, ultimately contributing to improved clinical management and outcomes.
Investigation of the Effect of Low-positive HER-2 on Neoadjuvant Chemotherapy Response in Hormone-positive Breast Cancer Patients
(Galenos Publ House, 2023) Karaboyun, Kubilay; Oznur, Meltem; Yolcu, Ahmet; Iriagac, Yakup; Seber, Selcuk
Objective: Recently, it has been suggested that low-positive human epidermal growth factor receptor-2 (HER-2) is a separate group of breast cancer. We examined the effect of low-positive HER-2 on neoadjuvant chemotherapy (NACT). Methods: This retrospective study included female patients aged >18 years who were diagnosed with histologically proven breast cancer between January 1, 2016, and January 1, 2020, and had breast surgery after NACT. Patients with triple-negative, estrogen receptor (<10%) weak positive, HER-2 immunohistochemical (IHC) scores 3+ or 2+/FISH-positive patients, and metastatic patients were excluded. Pathological complete response (pCR) was defined as the no invasive and in situ residue in the breast and lymph nodes in surgery after NACT. Results: One hundred twenty seven patients were included in this study. HER-2 IHC-score 0 patients were 55 (43.3%), 1+ patients were 52 (40.9%), and 2+ patients were 20 (15.7%). Nine (7.1%) patients showed a complete response to NACT. In the univariate analysis with clinicopathological variables of the patients to predict the complete response to NACT; estrogen receptor [odds ratio (OR): 0.97, 95% confidence interval (CI): 0.96-0.99, p=0.012], Ki-67 (OR: 1.12, 95% CI: 1.06-1.18, p<0.001), tumor grade (OR: 0.036, 95% CI: 1.13-30.36, p=0.036), and lymphovascular invasion (OR: 0.11, 95% CI: 0.01-0.93, p=0.043) showed the predictive features. In the multivariate analysis, Ki-67 (OR: 1.10, 95% CI: 0.04-1.17, p=0.001) was found to be an independent predictor of pCR. Conclusion: We determined that the low-positive-HER2 group has no effect on the treatment response in patients treated with NACT. We found that Ki-67 was an independent predictive for pCR.
Nanotechnology in oncology: a mini review
(Assoc Medica Brasileira, 2024) Cavdar, Eyyup; Karaboyun, Kubilay; Iriagac, Yakup
[No abstract available]
Neoadjuvan Kemoterapi Alan Meme Kanseri Hastalarında COVID-19 Pandemisinin Tanı ve Tedavi Sürecine Etkileri
(2021) Şeber, Erdoğan Selçuk; Çavdar, Eyyüp; İriağaç, Yakup; Karaboyun, Kubilay; Avcı, Okan
Amaç: Bu çalışmamızda neoadjuvan kemoterapi alan meme kanseri hastalarında pandeminin tanı-tedavi sürecine etkisini araştırdık.Gereç ve Yöntem: Koronavirüs hastalığı-2019 (COVID-19) pandemisi dönemindeki bir yıl ile pandemi öncesindeki 1 yılda neoadjuvan kemoterapialan hastaların klinikopatolojik özellikleri ile tanıdan operasyona kadar olan aşamaların süreleri karşılaştırıldı. Toplam 92 hasta retrospektif olarakanaliz edildi.Bulgular: Pandemi ve pandemi öncesi (prepandemik) dönemdeki hastaların klinikopatolojik özellikleri benzer bulundu. Pandemi dönemindeki hastasayısı 26 (%28,3) iken pandemi öncesi dönemde 66 (%71,7) idi. Tanı-tedavi sürelerinden patoloji raporlanma süresi, kemoterapi uygulanma süresi vepreoperatif hazırlık dönemi ve total süre iki dönem arasında benzerdi (sırasıyla; p=0,305, p=0,171, p=0,104, p=0,061). Manyetik rezonans raporlanmasüresi pandemi döneminde daha kısa saptandı (p=0,005).Sonuç: Neoadjuvan kemoterapi alan hastalarda meme kanserinin tanı ve tedavi süreleri pandemi döneminde, pandemi öncesi dönemle benzerdir.Yine de COVID-19 enfeksiyon riski düşünülerek hasta özelinde karar verilmelidir.
Prognostic factors influencing regorafenib treatment outcomes in metastatic colorectal cancer
(2023) Karaboyun, Kubilay; Yolcu, Ahmet
Aim: We aimed to determine the efficacy and prognostic factors of Regorafenib in advanced colorectal cancer patients. Materials and Methods: This study was designed as single-center and retrospective. The study included 72 patients with metastatic colorectal cancer treated with Regorafenib. Univariate and multivariate analyses of factors affecting survival were generated by Cox Regression Models. Results: Twenty-three (31.9%) of the patients were female, the median age was 65 years. The median progression-free survival (PFS) and overall survival (OS) were 4.13 and 8.7 months, respectively. The carcinoembryonic antigen (CEA) level (p=0.001), and Eastern Cooperative Oncology Group (ECOG) score (p<0.001) were found to be prognostic in the multivariate model for PFS. ECOG (p<0.001), CEA level (p<0.001), dose reduction (p=0.003), and side of the primary tumor (p=0.037) were prognostic for OS. Conclusion: Our study revealed that ECOG, requiring dose reduction during the treatment, and lower baseline CEA levels were found to be prognostic.
Prognostic Role of Lymphovascular Invasion and Perineural Invasion in Breast Cancer Treated with Neoadjuvant Chemotherapy
(Akad Doktorlar Yayinevi, 2022) Çavdar, Eyyüp; İriağaç, Yakup; Karaboyun, Kubilay; Avcı, Okan; Öznur, Meltem; Şeber, Erdoğan Selçuk
In our study, we investigated the predictive properties of LVI (lymphovascular invasion) and PNI (perineural invasion) on survival times from pathology specimens obtained from surgical operation after neoadjuvant chemotherapy (NAC) with breast cancer patients. Two hundered eleven female patients were included in this study. We evaluated the relationship between potential prognostic factors and mean recurrence-free survival (RFS) and overall survival (OS) times using Kaplan-Meier methodology and Cox proportional hazard modelling.The mean follow-up time was 27.3 months.PNI positive patients had shorter RFS and OS times than PNI negatives (p< 0.001, p= 0.002, respectively), and LVI positive patients had shorter RFS and OS times than LVI negatives (p< 0.001, p< 0.001, re-spectively). In the multivariate analysis performed, the presence of pN stage and PNI were found to be predictive for RFS (p= 0.047, p< 0.001, respectively), while pT stage and PNI positivity were found to be predictive for OS (p= 0.035, p= 0.017, respectively). LVI did not show the property of being an independent predictive marker for survival. PNI caused significant survival differences in all subtypes for both RFS (log-rank p< 0.001, p= 0.003, p= 0.001, respectively) and OS(log-rank p= 0.035, p= 0.006, p= 0.020 respectively) in HR+/Her2-, Her2+ and Triple negative breast cancer subtyping. LVI, on the other hand, caused survival distribution difference for RFS (p= 0.021) in the HR+/Her2-subtype and for both RFS and OS in the Triple-negative subtype (p< 0.001, p= 0.025, respectively). PNI is strongly and significantly associated with RFS and OS. We suggest that it can be used in identifying high-risk patients for recurrence of PNI and in new staging systems.
PROPSEA, safety evaluation of palbociclib and ribociclib in older patients with breast cancer: A prospective real-world TOG study
(Elsevier, 2023) Avci, Okan; Iriagac, Yakup; Cavdar, Eyyuep; Karaboyun, Kubilay; Araz, Murat; Sakalar, Teoman; Degerli, Ezgi
Introduction: In this study, the toxicities and management of palbociclib and ribociclib in older patients (>= 65 years) with metastatic breast cancer patients were investigated.Materials and Methods: Among older patients receiving palbociclib and ribociclib, Geriatric 8 (G8) and Groningen Frailty Index were used to evaluate frailty status. Dose modifications, drug withdrawal and other serious adverse events (SAEs) were recorded and analyzed according to baseline patient characteristics.Results: A total of 160 patients from 28 centers in Turkey were included (palbociclib = 76, ribociclib = 84). Forty-three patients were >= 75 years of age. The most common cause of first dose modification was neutropenia for both drugs (97% palbociclib, 69% ribociclib). Liver function tests elevation (10%) and renal function impairment (6%) were also causes for ribociclib dose modification. Drug withdrawal rate was 3.9% for palbociclib and 6% for ribociclib. SAEs were seen in 11.8% of those taking palbociclib and 15.5% of those on riboclib. An ECOG performance status of >= 2 and being older than 75 years were associated with dose reductions. Severe neutropenia was more common in patients with non-bone-only metastatic disease, those receiving treatment third-line therapy or higher, coexistance of non-neutropenic hematological side effects (for ribociclib). Neutropenia was less common among patients with obesity.Discussion: Our results show that it can be reasonable to start palbociclib and ribociclib at reduced dose in patients aged >= 75 years and/or with an ECOG performance status >= 2.
Prospective comparison of the value of CARG, G8, and VES-13 toxicity tools in predicting chemotherapy-related toxicity in older Turkish patients with cancer
(Elsevier, 2022) Çavdar, Eyyüp; İriağaç, Yakup; Karaboyun, Kubilay; Avcı, Okan; Şeber, Erdoğan Selçuk
Background: In older patients with cancer, it is very important to choose the appropriate treatment because they are at high risk for chemotherapy toxicity. Our study investigated characteristics of Cancer and Aging Research Group (CARG), Geriatric 8 (G8), and Vulnerable Elders Survey (VES-13) screening tools for predicting chemotherapy-related toxicity (CRT) prospectively.Materials and methods: 208 patients aged >= 65 years old for whom chemotherapy was planned to treat non -haematological cancer between February 2021-September 2021 were included in the study. The CARG, G8, and VES-13 toxicity tools were completed by the oncologist through face-to-face interviews before starting the first chemotherapy treatment. CRTs during chemotherapy were evaluated according to the National Cancer Insti-tute's Common Terminology Criteria for Adverse Events v4.03. Logistic regression models, the area under the re-ceiver operating characteristic curve (ROC-AUC), and correlation analyses were used for comparing questionnaires.Results: Median age was 70.4 (range 65-86) years. Of the participants, 103 (49.5%) participants experienced grade 3-5 CRT (32.2% haematological, 28.4% non-haematological) during chemotherapy. ROC-AUC value of CARG was determined as 0.827 (95% CI [confidence interval]: 0.77-0.88, p < 0.001), it was determined as 0.744 (95% CI: 0.68-0.81, p < 0.001) for G8 and 0.726 (95% CI: 0.66-0.80, p < 0.001) for VES-13. In the univariate regression analysis, CARG (OR [odds ratio] = 13.57, 95% CI: 6.0-30.72, p < 0.001), G8 (OR = 3.19, 95% CI: 1.62-6.29, p = 0.001), and VES-13 (OR = 9.5, 95% CI: 5.01-17.89, p < 0.001) were found to be predictive for CRT. The multivariate analysis (included stage, Eastern Cooperative Oncology Group [ECOG] performance status, presence of comorbid disease, platinum-based treatment regimen, taxane-based treatment regimen, CARG, VES-13, G8) showed that CARG (OR =12.08, 95% CI: 5.11-28.56, p < 0.001), VES-13 (OR =10.06, 95% CI: 4.92-22.98, p < 0.001), and G8 (OR = 2.20, 95% CI: 1.04-4.69, p = 0.040) screening tools were strong predictors for CRT. The CARG and VES-13 questionnaires were predictive for reducing the initial treatment dose (p = 0.004, p = 0.004, respectively), interruption of treatment (p < 0.001, p < 0.001, respectively), discontinuing treatment (p = 0.002, p = 0.002, respectively), and unexpected hospitalisation (p = 0.012, p = 0.003, respectively).Conclusions: We showed that all three CARG, G8, and VES-13 questionnaires are helpful tools in the decision -making process for ideal chemotherapy to predict severe CRT; however, CARG and VES-13 questionnaires appear more useful in daily oncology practice than the G8 questionnaire. (c) 2022 Elsevier Ltd. All rights reserved.
Soluble B7H3 level in breast cancer and its relationship with clinicopathological variables and T-cell infiltration
(Termedia Publishing House Ltd, 2022) Avcı, Okan; Çavdar, Eyyüp; İriağaç, Yakup; Karaboyun, Kubilay; Çelikkol, Aliye; Kurtoğlu Özçağlayan, Tuğba İlkem; Öznur, Meltem; Gürdal, Sibel Özkan; Şeber, Erdoğan Selçuk
Aim of the study Although early diagnosis of breast cancer (BC) is often associated with a good prognosis, there is currently no biomarker with high sensitivity serving this purpose. B7H3, a recently identified member of the B7 family, appears to inhibit antitumor immunity. We investigated the soluble B7H3 (sB7H3) level in BC and its relationship with clinicopathological variables and stromal tumor-infiltrating lymphocytes (sTILs). Material and methods: The study which was designed as a cross-sectional trial between January 2020 and September 2021, included 93 BC patients, 20 patients with benign breast disease (BBD) and 14 healthy volunteers as the control group. Serum sB7H3 levels were measured using the ELISA (enzyme-linked immunosorbent assay) method and sTlLs were measured by immunohistochemistry using Tru-cut biopsy materials. Results: sB7H3 levels in BC patients were significantly higher than those in patients with BBD and healthy volunteers. Receiver operating characteristic curve analysis results showed that sB7H3 level may be a potential biomarker for distinguishing patients with BC from those with BBD (AUC: 0.807; sensitivity: 0.786; specificity: 0.706) and from healthy volunteers (AUC: 0.731; sensitivity: 0.700; spedicity: 0.692). Conclusions: To the best of our knowledge, the present study is the first to investigate the relationship between sB7H3 and disease parameters in BC. We found that sB7H3 may be a clinically practical and meaningful biomarker in differentiating BC from BBD. In order to evaluate the relationship of B7H3 with clinical variables in BC, and especially with sTILs, tissue-based studies with higher numbers of patients are needed.
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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