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Cem Mirili,1 Semra Paydaş,1 Isa B Guney,2 Ali Ogul,1 Serkan Gokcay,1 Mahmut Buyuksimsek,1 Abdullah E Yetisir,1 Bilgin Karaalioglu,1 Mert Tohumcuoglu,1 Gulsah Seydaoglu3 1Department of Medical Oncology, Çukurova University Faculty of Medicine, Adana, Turkey; 2Department of Nuclear Medicine, Çukurova University Faculty of Medicine, Adana, Turkey; 3Department of Bioistatistics, Çukurova University Faculty of Medicine, Adana, Turkey Purpose: The aim of this study was to evaluate the prognostic and predictive value of neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (DNLR), lymphocyte-to- monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) in soft tissue sarcoma (STS) cases treated with pazopanib. Materials and methods: The study population included 26 STS cases treated with pazopanib for at least 3 months. NLR, DNLR, LMR, and PLR were evaluated at baseline, and at third month of therapy and also compared with response to pazopanib. Median measurements were taken as cutoff for NLR (4.8), DNLR (3.1), LMR (3.6), and PLR (195). The associations between these cutoff values and survival times (progression-free survival [PFS] and overall survival [OS]) were assessed by Kaplan–Meier curves and Cox proportional models. Results: Patients with low pretreatment NLR and DNLR had longer OS (P=0.022, P=0.018), but low PLR was found to be associated only with longer OS. Additionally, decrease in NLR and DNLR after 3 months of therapy as compared with pretreatment measurements was found to be associated with an advantage for OS (P=0.021, P=0.010, respectively) and PFS (P=0.005, P=0.001, respectively). Response to pazopanib; changes in NLR, DNLR, LMR, and PLR; and >3 metastatic sites were found to be independent risk factors in univariate analysis, but NLR was the only independent risk factor in multivariate analysis. Conclusion: Low pretreatment and decrease in NLR and DNLR values, and regression/stable disease after 3 months of pazopanib are predictive factors for longer OS and PFS. Keywords: soft tissue sarcoma, STS, pazopanib, angiogenesis, inflammation, neutrophil-to-lymphocyte ratio, NLR, derived neutrophil-to-lymphocyte ratio, DNLR

Several studies demonstrated the utility of plasma-based cell-free circulating tumor DNA (ccfDNA) in determination of mutations in non-small cell lung cancer (NSCLC). We aimed to report our results of next generation sequencing (NGS) using liquid biopsy in patients with NSCLC. Patients with advanced stage NSCLC were enrolled and their genomic profiling results were recorded. Next generation sequencing targeted panel includes 19 hot-spot genes. The plasma was separated from the peripheral blood sample and ccfDNAs were isolated for NGS. We performed genomic profiling in 100 patients (20 females and 80 males) with a median age of 59.3 (range 26-79). A second liquid biopsy was performed in eight patients who developed progressive disease after the first treatment. The study population had adenocarcinoma (AC) (n = 73), squamous cell carcinoma (SCC) (n = 14), or NSCLC-NOS (not otherwise specified) (n = 13). In the SCC group, three of 14 patients had variants on EGFR and MET genes. In the AC and NSCLC-NOS groups, 39 out of 86 patients (45.3%) had variants. The most common one was in the EGFR gene (n = 27, 31.4%) including seven mutations related to drug resistance and two were polymorphisms. Three patients had both driver and resistance mutations (EGFR T790M, n = 2; KRAS exon 2 G12S and MET exon 14 E1012K, n = 1). Fifteen patients (17.4%) had an activating EGFR mutation and eight patients (9.3%) had variants in the KRAS gene. We reported our results regarding genomic profiling related to treatment using liquid biopsy in patients with NSCLC. Advantages of this method are the non invasiveness and reproducibility.

We aimed to evaluate the efficacy and safety of trastuzumab emtansine in patients with metastatic breast cancer previously treated with pertuzumab plus trastuzumab and taxane. We reviewed the medical records of patients who were diagnosed with Human Epidermal Growth Factor Receptor 2 (HER-2) positive metastatic breast cancer and received pertuzumab and then TDM-1 between January 2014 and January 2021 from twenty- five cancer centers. The Kaplan- Meier method estimated progression-free survival (PFS) and overall survival (OS). Additionally, objective response rate (ORR), clinical benefit rate (CBR), and safety were evaluated. One hundred fifty-three patients were included,79.1% of the patients received TDM-1 in the second line, 90.8% had visceral metastasis, and 30.7% had central nervous system involvement. The PFS and OS of TDM-1 were evaluated according to the number of previous lines (on the 2nd line or more than two lines) metastatic sites (visceral and non-visceral) and the presence of central nervous metastasis. In TDM-1 therapy, PFS in second line therapy was ten months (95% CI: 7.7 - 12.2); this was statistically higher than later-line PFS, which was six months (95% CI: 3.3 to 8.6) ( p  = 0.004). The median OS time was 25 months (95% CI: 21.0 to 28.9) in patients treated with TDM-1 in the second line and 19 months (95% CI: 12.3 to 25.6) in patients who received later than the second line( p  = 0.175). There were no significant differences in PFS time of patients with and without visceral and central nervous metastases. Our study showed that TDM-1 was also effective in patients using pertuzumab, contributes significantly to PFS when used in the second line compared to its use in the later line, and does not make any difference in OS.

Objective: The study aims to investigate the estrogen-agonistic effects of tamoxifen on voice parameters in premenopausal women diagnosed with breast cancer., Methods: A total of 108 premenopausal women were included, segmented into distinct treatment groups and a control group. Objective sound analysis was conducted using robust statistical methods, employing SPSS 25.0 for data analysis., Results: The study identified a statistically significant reduction in Jitter values across all treatment groups compared to the control group. No significant changes were observed in other voice quality parameters such as F0, Shimmer, NHR, and HNR., Conclusions: The findings suggest that tamoxifen may have an estrogen-agonistic effect on voice quality, thereby potentially influencing future treatment protocols. This research fills a critical void in existing literature and sets the stage for more comprehensive studies that consider affects of hormonal therapies to voice., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: To evaluate the relationship of overall survival (OS) and progression-free survival (PFS) with the derived neutrophil-lymphocyte ratio (dNLR), neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), and platelet-lymphocyte ratio (PLR) in patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC)., Methods: The study included 43 patients with EGFR-mutant metastatic NSCLC. The dNLR, NLR, LMR, and PLR values were calculated using the baseline complete blood counts before and after treatment with erlotinib., Results: The NLR value had the best diagnostic test performance with a sensitivity of 91.3%. dNLR, NLR, LMR, and PLR were found to be significant for the prediction of OS and PFS. While the delta dNLR and NLR values were significant for OS, only the delta NLR value was significant for PFS., Conclusions: The dNLR, NLR, LMR, and PLR values were found to be significant in the prediction of OS and PFS in erlotinib-treated metastatic NSCLC. Further clinical studies are needed to determine the ideal target-specific tyrosine kinase inhibitor in cases of metastatic NSCLC presenting with the EGFR-activating mutation., (Copyright © 2023 Copyright: © 2023 Journal of Cancer Research and Therapeutics.)

Introduction: This study aims to report the efficacy and safety of capecitabine plus temozolomide (CAPTEM) across different lines of treatment in patients with metastatic neuroendocrine tumors (NETs)., Methods: We conducted a multicenter retrospective study analyzing the data of 308 patients with metastatic NETs treated with CAPTEM between 2010 and 2022 in 34 different hospitals across various regions of Turkey., Results: The median follow-up time was 41.0 months (range: 1.7-212.1), and the median age was 53 years (range: 22-79). Our results across the entire patient cohort showed a median progression-free survival (PFS) of 10.6 months and a median overall survival (OS) of 60.4 months. First-line CAPTEM treatment appeared more effective, with a median PFS of 16.1 months and a median OS of 105.8 months (median PFS 16.1, 7.9, and 9.6 months in first-, second- and ≥third-line respectively, P = .01; with median OS values of 105.8, 47.2, and 24.1 months, respectively, P = .003) In terms of ORR, the first-line treatment again performed better, resulting in an ORR of 54.7% compared to 33.3% and 30.0% in the second and third or higher lines, respectively (P < .001). Grade 3-4 side effects occurred only in 22.5% of the patients, leading to a discontinuation rate of 9.5%. Despite the differences in outcomes based on treatment line, we did not observe a significant difference in terms of side effects between the first and subsequent lines of treatment., Conclusions and Relevance: The substantial superior outcomes in patients receiving first-line CAPTEM treatment highlight its potential as an effective treatment strategy for patients with metastatic NET., (© The Author(s) 2023. Published by Oxford University Press.)

Objective: Breast cancer is the most common malignancy in women. In the treatment of these patients, pathological complete response is defined as the absence of invasive cancer in breast or lymph node tissue after the completion of neoadjuvant chemotherapy. In this study, we aimed to investigate the relationship of enhancer of zeste homolog 2 and mucin 1 expressions with pathological complete response in patients with breast cancer receiving neoadjuvant chemotherapy., Methods: A total of 151 patients were included in the study. Enhancer of zeste homolog 2 and mucin 1 expressions were evaluated in the biopsy materials pre-neoadjuvant chemotherapy and post-neoadjuvant chemotherapy surgical material, and their relationship with pathological complete response was investigated., Results: The pathological complete response rates were significantly higher among the hormone receptor-negative patients, those with a high Ki-67 score, and patients with HER2-positive. Higher pathological complete response rates were obtained from patients with enhancer of zeste homolog 2 expression positivity pre-neoadjuvant chemotherapy. In addition, after neoadjuvant chemotherapy, enhancer of zeste homolog 2 expression was found to be completely negative in materials with pathological complete response; that is, in breast tissues considered to be tumor-free. While there was no significant relationship between mucin 1 expression and pathological complete response pre-neoadjuvant chemotherapy, mucin 1 expression was determined to significantly differ between the tissues with and without pathological complete response among the surgical materials examined., Conclusion: In our study investigating the relationship between enhancer of zeste homolog 2 and mucin 1 expression and pathological complete response in patients who received neoadjuvant chemotherapy, we found that enhancer of zeste homolog 2 expression could be used as a predictive marker for pathological complete response. However, mucin 1 expression was not associated with pathological complete response.

This study aimed to evaluate CD73 and PD-L1 and determine their relationship with each other and with overall survival (OS) in sarcoma patients. The paraffin blocks of 101 patients were analysed. 56.4% were female, and the mean age was 51.39 years. The mean OS was 20.73 months, and the Ki-67 proliferative index was 41.45. A positive correlation was found between CD73 tumour and CD73 tumour-infiltrating lymphocyte (TIL) findings. CD73 tumour and TIL findings were also positively correlated with PD-L1 percentages and PD-L1 intensity. An inverse correlation was detected between OS and CD73 tumour and TIL groups of 5-25%, 25-50%, 50-75%, 75-90%, and > 90%, but no such correlation was found for the ≤ 5% group. There was an inverse correlation between OS and the PD-L1 percentages of  50% and the PD-L1 intensity of weak-moderate and strong, but no correlation was found for the negative values. Lastly, an inverse correlation was found between OS and the Ki-67 proliferative index. We found CD73 and PD-L1 positivity to be associated with decreased OS in sarcoma patients and determined a significant correlation between these parameters. This result is promising in terms of achieving better survival and disease control with anti-CD73 and anti-PD-L1 therapy in selected patients.

Aim: The aim of this study is to evaluate the efficacy and toxicity of trastuzumab emtansine (T-DM1) in cases with metastatic breast cancer (mBC) in different lines of treatment., Method: Retrospective analysis of T-DM1 results of human epidermal growth factor receptor 2 (Her2) positive 414 cases with mBC from 31 centers in Turkey., Findings: Except 2, all of the cases were female with a median age of 47. T-DM1 had been used as second-line therapy in 37.7% of the cases and the median number of T-DM1 cycles was 9. Progression-free survival (PFS) and overall survival (OS) times were different according to the line of treatment. The median OS was found as 43, 41, 46, 23 and 17 months for 1st, 2nd, 3rd, 4th and 5th line, respectively ( p  = 0.032) while the median PFS was found as 37, 12, 8, 8 and 8 months, respectively ( p  = 0.0001). Treatment was well tolerated by the patients. The most common grade 3-4 adverse effects were thrombocytopenia (2.7%) and increased serum gamma-glutamyl transferase (2%)., Discussion: The best of our knowledge this is the largest real-life experience about the safety and efficacy of T-DM1 use in cases with mBC after progression of Her2 targeted treatment. This study suggests and supports that T-DM1 is more effective in earlier lines of treatment and is a reliable option for mBC.

Objective: Bone marrow infiltration (BMI) affects the stage diagnosis, and treatment of lymphoma. We aimed to evaluate the performance of bone marrow biopsy (BMB) and positron emission tomography-computed tomography (PET/CT) in detecting BMI in lymphoma patients., Materials and Methods: A total of 269 non-Hodgkin’s lymphoma (NHL) and 110 Hodgkin’s lymphoma (HL) patients were evaluated retrospectively. Sensitivity, negative predictive value (NPV), and accuracy were calculated for PET/CT and BMB in detecting BMI.ensitivity, negative predictive value (NPV) and accuracy were calculated for PET/CT and BMB in detecting BMI., Results: Sensitivity, NPV, and accuracy for PET/CT in detecting BMI in NHL cases were 65%, 78%, and 84.4%, respectively, while they were 55%, 73.4%, and 79.9% for BMB. PET/CT performance for diffuse large B-cell lymphoma and follicular lymphoma was better than that of BMB, whereas the performance of BMB was better for mantle-cell lymphoma, Burkitt’s lymphoma, and primary mediastinal B-cell lymphoma. Sensitivity, NPV, and accuracy for PET/CT in HL cases were 91.3%, 97.75%, and 98.18%, respectively, while they were 56.52%, 89.69%, and 90.91% for BMB. Due to BMB, 43 (15.9%) patients in the NHL group and 2 (1.8%) patients in the HL group were protected from downstaging., Conclusion: Although their results vary according to NHL subtypes, PET/CT and BMB are complementary methods in determining BMI. In HL, PET/CT is an important diagnostic tool for detecting BMI, and BMB is not necessary in a significant proportion of cases.

Objective: Response to neoadjuvant chemotherapy (NAC) is predictive for survival times in some patients with breast cancer (BC). The aim of this study is to explore the predictive value of some inflammatory markers including neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), monocyte-to-high density lipoprotein ratio (MHR) and prognostic nutritional index (PNI) in cases with BC treated with NAC., Materials and Methods: One hundred and ten patients with BC treated with NAC were included in the study. Measurements for NLR, dNLR, MHR and PNI were calculated with available formulas. The value of NLR, dNLR, MHR and PNI in predicting pCR to NAC in BC was analyzed using receiver operating characteristic (ROC) curve analysis. All analyses were performed using the SPSS statistical software package (SPSS statistics 21.0)., Results: Mean NLR values were 2.2±0.8 vs. 2.6±1.3 for pCR (+) and pCR (-) groups (p=0.603). Mean dNLR values were 1.5±0.5 vs. 1.9±0.8 for pCR (+) and pCR (-) groups, respectively and this was statistically significant (p=0.022). Mean MHR values were 15.4±17.2 vs. 13.2±10.1 for pCR (+) and pCR (-) groups (p=0.406). Mean PNI values were 52±5.1 vs. 49±5.8 for pCR (+) and pCR (-) groups, and this was statistically significant (p=0.015). In multiple logistic regression analysis PNI was found to be independent factor for pCR., Conclusion: In this study pre-treatment dNLR and PNI were found to be predictive for pCR while NLR and MHR were not found to be associated with pCR. PNI and dNLR are simple but useful biomarkers predicting response to NAC., Competing Interests: Conflict of Interest: The authors have no conflicts of interest to declare., (Copyright © 2020 Turkish Federation of Breast Diseases Associations.)

Introduction: Mesothelioma is an aggressive tumour that originates in serous surfaces. The primary end point of this study was to invastigate the relationship of progression free survival (PFS) and overall survival (OS) with the c-Met, EGFR, PTEN, PDGFR-alpha, PI3K/AKT and mTOR expression levels in the tumour tissue of pleural and peritoneal mesothelioma cases., Materials and Methods: The study included 53 patients diagnosed with mesothelioma between 2005 and 2016. The cases were separated into 2 groups as pleural and peritoneal. The effects on OS and PFS were examined of the c-Met, EGFR, PTEN, PDGFR-alpha, PI3K/AKT and mTOR expression levels and also clinicopathological parameters and the treatments given. In the statistical analysis of the data obtained, IBM SPSS vn 20.0 software was used., Result: Of the 53 patients included in the study, 39 (73.6%) were diagnosed with pleural mesothelioma and 14 (26.4%) with peritoneal mesothelioma. According to the c-Met and mTOR expression, OS and PFS of the peritoneal cases with high expression (2+, 3+) was seen to be significantly better than that of the peritoneal cases with low expression (0, 1+) (p<0.05). According to the PDGFR expression, OS and PFS of the pleural cases with low expression (0, 1+) was seen to be significantly better than that of the pleural cases with high expression (2+, 3+) (p<0.05)., Conclusions: The examination of c-MET, PDGFR-alpha and m-TOR expression in the in the tumor tissue of mesothelioma cases may be important in determining prognosis.

Background: Thyroid cancer is the most common endocrine cancer, with an increasing incidence around the world in the last three decades. The increased risk of secondary cancer is associated with a genetic predisposition or radioactive iodine used in the treatment., Case Report: A 65-year old male patient was operated on for thyroid papillary cancer. He received radioactive iodine on two occasions postoperatively. After six years, he presented with malaise and fatigue with leukocytosis and eosinophlilia. The physical examination revealed inguinal lymphadenopathies and splenomegaly, after examining the bone marrow and lymph node biopsies, he was diagnosed with eosinophilic myeloproliferative neoplasia and T-cell lymphoblastic leukaemia/lymphoma., Conclusion: Leukaemia and other haematological malignencies may develop after radioactive iodine treatment. Patients with radioactive iodine ablation history should be monitored for a long time.