Tirozin Kinaz İnhibitörleri ile Tedavi Edilen Metastatik Renal Hücreli Karsinom Hastalarında Prognostik Nütrisyonel İndeksin Prognostik Önemi

Amaç: Bu çalışmada; birinci basamak hedefli tedavi olarak pazopanib veya sunitinib alan metastatik renal hücreli kanser (mRCC) hastalarında tedavi öncesi Prognostik Nütrisyonel İndeksi’nin (PNİ) prognostik rolünü değerlendirmeyi amaçladık. Gereç ve Yöntem: mRCC’li 77 hastanın tedavi modaliteleri, demografik, klinik ve patolojik özellikleri geriye dönük olarak incelendi ve PNİ hesaplandı. Ortanca değere göre hastalar düşük ve yüksek prognostik nütrisyonel indeks gruplarına ayrıldılar. Sağkalım analizi için Kaplan-Meier yöntemi, tek değişkenli ve çok değişkenli analiz için Cox-regresyon analizi kullanıldı. Bulgular: Tüm hastalar için genel medyan progresyonsuz sağkalım (PFS) ve genel sağkalım (OS) süresi sırasıyla 15 ay [%95 güven aralığı (GA): 10,9-19,1 ay] ve 27 ay (%95 GA: 15,9-38,1 ay) olarak saptandı. Düşük PNİ’si olan hastalarda, yüksek PNİ’si olan hastalara göre anlamlı olarak daha kısa medyan PFS (11’e karşı 20 ay, p=0,001) ve OS (17’ye karşı 40 ay, p=0,001) saptandı. Çok değişkenli analizde PNİ, hem OS hem de PFS üzerinde bağımsız bir öngörücü olarak gösterildi, ayrıca Eastern Cooperative Oncology Group-Performance Status OS için bağımsız bir öngörücü iken, International Metastatic RCC Database Consortium skoru ise PFS için bağımsız bir öngörücü belirteç olarak gösterildi. Sonuç: Düşük PNİ, birinci basamak tedavi olarak tirozin kinaz inhibitörleri alan mRCC hastalarında sağkalım için önemli bir öngörücü belirteç olabilir

Next generation sequencing analysis of BRCA1 and BRCA2 identifies novel variations in breast cancer

Mutations in two major breast cancer susceptibility genes, BRCA1 and BRCA2, have been identified to be the most important predisposing factors for the development of breast cancer. Thus, BRCA1/2 testing is a well-established method of choice for the assessment of developing breast cancer. Accordingly, here we aimed to report novel BRCA1/2 variations and distribution of previously known mutations and their association with the clinical course of breast cancer disease. A total of 287 breast cancer patients were enrolled from January 2017 through December 2019. Of these patients, 50 of them were identified to be positive for BRCA1/2. Next Generation Sequencing analysis was performed for the screening of exonic and intronic variations of BRCA1/BRCA2 genes. Notably, novel variations of 4448 G > A (Ser1843Asn) in BRCA1, and 982dupA (Thr328AspfsTer) and 7588C > T (Gln2530Ter) in BRCA2 gene were identified. The most common variations in BRCA1 gene were 5152 + 66G > A, 442-34C > T and 5266dupC. In BRCA2 gene, the most common variations were 9097dupA, 67 + 1G > A and 1114A > C. Novel variations of BRCA1 and BRCA2 genes were identified in breast cancer and might be useful predisposing factors in breast cancer diagnosis. © 2020 Elsevier Inc

Nivolumab for metastatic uveal melanoma: a multicenter, retrospective study

Systemic treatment options with proven efficacy for the treatment of metastatic uveal melanoma are limited. In this study, we aimed to evaluate the efficacy of nivolumab in metastatic uveal melanoma patients. In our multi-center study, the files of patients who received nivolumab treatment with a diagnosis of metastatic uveal melanoma were retrospectively reviewed and their information was recorded. Seventeen patients were enrolledand 16 patients were evaluable for efficacy. The objective response rate (ORR) was 18% including one confirmed complete response and two confirmed partial responses. The median progression-free survival (PFS) was 5.8 months (95% CI, 0.03-11.57 months), and the median overall survival (OS) was 10.5 months (95% CI, 3.87-14.14 months). Significant longer OS and PFS were observed in patients with the performance status of the Eastern Cooperative Oncology Group (ECOG-PS) 0. Although significant longer OS was detected in patients with low median lactate dehydrogenase (LDH) levels, no significant difference was found in PFS. Grade 1 and 2 fatigue and decreased appetite were the most common side effects associated with treatment (17%); grade 3 and 4 side effects were not observed. Immunotherapy is also emerging as a treatment option among the limited number of treatment options in metastatic uveal melanoma (mUM), but its efficacy needs to be demonstrated with prospective studies involving a larger number of patients

A new predictive marker for predicting response after neoadjuvant chemotherapy in hormone receptor positive/HER2-negative patients: a logarithmic model

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

PROPSEA, safety evaluation of palbociclib and ribociclib in older patients with breast cancer: A prospective real-world TOG study

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