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.
Random Forest (RF), a mostly model-free and robust machine learning method, has been successfully applied to right-censored survival data, under the name of Random Survival Forest (RSF). However, RF/RSF has its distinct strategies in classification and prediction. First, it is an ensemble classifier and its performance is an average of multiple rounds of data fitting. Second, the training set is a bootstrap (sampling with replacement) generated set with repeated used of roughly 2/3 of all samples and testing set consists of those not used (out of bag samples). Both features are not intrinsic to Cox regression or other single classifiers. Not considering these two features could potentially lead to a partial comparison between the performance of the two methods. By using a colorectal survival dataset, we illustrate the problems of using k-fold cross-validation, using only one resampling without an ensemble average, and using the whole dataset for both fitting and testing, in Cox regression, when comparing with RSF. We provide a more accessible R code for simple calculation of discordance index (D-index) and unweighted integrated Brier score (IBS) for Cox regression, and unweighted IBS for RSF. Doi: 10.28991/SciMedJ-2021-0301-9 Full Text: PDF
Thyroid hormones increase the hepatic glyconeogenesis, glycogenolysis and the absorption of glucose. Glucose intolerance is common in thyroid dysfunction. HbA1c is the most important determinant of long term glysemic status in diabetic patients. HbA1c is affected from various factors. In this study we evaluated the relation between thyroid function tests and HbA1c in non-diabetic patients with thyroid dysfunction. Non-diabetic 43 patients with hyperthyroidism, 20 patients with hypothyroidism and for control group 29 euthyroid patients which appealed to Ankara Numune Training and Research Hospital Internal Outpatient Clinic between June 2008 and January 2009 were recruited to this study. Fasting blood sugar, urea, creatinine, hemoglobine, HbA1c, TSH, FT3, FT4 and albumine levels of all of the patients that recruited to study were determined. There was no statistically significant difference for the mean age (p=0.271) and gender distribution (p=0.23) in the cases of hyperthyroidism, hypothyroidism and euthyroid controls. HbA1c levels were significantly higher in hyperthyroid group when compared to hypothyroid and euthyroid groups (p<0,001). Fasting blood glucose levels were found significantly higher in hyper thyroid group than hypothyroid and euthyroid groups (p=0.018). A positive correlation was revealed between the increasing age and HbA1c levels. A statistically significant difference was found in the levels of HbA1c values in patients with hyperthyroidism according to euthyroid and hypothyroid patients and this finding is in compliance with the results of current literature. This makes us to think that here is a relation between insulin resistance and hyperthyroidism. Therefore, it is suggested that monitorisation of blood glucose levels regularly is useful for the early diagnose of type II diabetes mellitus in patients with hyperthyroidism, both during the therapy and post treatment period. Keywords: Thyroid dysfunction, HbA1c, Insulin resistance Özet Tiroid hormonları hepatikglukoneogenezi, glikojenolizi ve intestinal glukoz emilimini arttırırlar. Tiroid disfonksiyonunda glukoz intoleransı sıkça karşılaşılan bir durumdur. HbA1c diyabetik hastalarda uzun süreli glisemik durumun değerlendirilmesinde en önemli belirteçdir. HbA1c düzeyi ise çeşitli faktörlerden etkilenebilmektedir. Biz bu çalışmamızda diyabetik olmayan yeni tanı konmuş tedavi almamış tiroid disfonskiyonu olan hastalarda tiroid fonksiyon testleri ve HbA1c arasındaki ilişkiyi inceledik. Bu çalışma Ankara Numune Eğitim ve Araştırma Hastanesi Dahiliye polikliniklerine ( Haziran -2009 Ocak) başvuran diyabetik olmayan ve ilk kez tanı alan 43 hipertiroidi ve 20 hipotiroidi hastasıyla 29 ötiroidili kontrol grubu arasında yapıldı. Çalışmaya katılan tüm olguların açlık kan şekeri, üre, kreatinin, hemoglobin, HbA1c, TSH, FT3, FT4, albümin değerlerine bakıldı. Hipertiroidi, hipotiroidi ve ötiroidi olguların yaş ortalamaları (p=0,271) ve cinsiyet dağılımları (p=0,23) açısından istatiski olarak anlamlı fark bulunmadı. Hipertiroidi grubunda HbA1c sev...
Objectives Colorectal carcinomas are the third-most common tumors in the world, and colorectal cancer ranks second in cancer-related deaths. Our aim in this study was to investigate the correlation between programmed cell death ligand 1 (PD-L1) expression and clinicopathologic parameters in colorectal carcinomas and their relationship to the tumor immune microenvironment, epithelial-mesenchymal transition (EMT), and microsatellite instability. We also investigated the predictive and prognostic role of PD-L1. Methods One hundred patients with a diagnosis of colorectal adenocarcinoma who did not receive neoadjuvant therapy were included in the study. The relationships among the altered expression of PD-L1; vimentin; E-cadherin; mismatch repair status; and pathologic microenvironmental features, including the presence of tumor budding and CD8-positive tumor infiltrating lymphocytes (TILs), were assessed. Results Increased PD-L1 expression in tumor cells was associated with increased TILs (P = .013), high histologic grade (P = .011), advanced pathologic T stage (P = .007), lymph node metastasis (P = .002), distant metastasis (P < .001), perineural invasion (P = .009), high bud score (P = .023), EMT (P < .001), and shorter disease-free survival (P = .029). Conclusions Overall, PD-L1 expression in colorectal carcinoma tumor cells is a marker of poor prognosis, and the positive correlation detected between EMT status and PD-L1 expression suggests that patients with the mesenchymal phenotype may be more likely to benefit from programmed cell death 1 protein/PD-L1 immunotherapy.
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