Treatment outcomes and prognostic factors in patients with driver mutant non-small cell lung cancer and de novo brain metastases.

Central nervous system (CNS) metastases can be seen at a rate of 30% in advanced stages for patients with non-small cell lung cancer (NSCLC). Growing evidence indicates the predictive roles of driver gene mutations in the development of brain metastases (BM) in recent years, meaning that oncogene-driven NSCLC have a high incidence of BM at diagnosis. Today, 3rd generation targeted drugs with high intracranial efficacy, which can cross the blood-brain barrier, have made a positive contribution to survival for these patients with an increased propensity to BM. It is important to update the clinical and pathological factors reflected in the survival with real-life data. A multi-center, retrospective database of 306 patients diagnosed with driver mutant NSCLC and initially presented with BM between between November 2008 and September 2022 were analyzed. The median progression-free survival (mPFS) was 12.25 months (95% CI, 10-14.5). While 254 of the patients received tyrosine kinase inhibitor (TKI), 51 patients received chemotherapy as first line treatment. The median intracranial PFS (iPFS) was 18.5 months (95% CI, 14.8-22.2). The median overall survival (OS) was 29 months (95% CI, 25.2-33.0). It was found that having 3 or less BM and absence of extracranial metastases were significantly associated with better mOS and iPFS. The relationship between the size of BM and survival was found to be non-significant. Among patients with advanced NSCLC with de novo BM carrying a driver mutation, long-term progression-free and overall survival can be achieved with the advent of targeted agents with high CNS efficacy with more conservative and localized radiotherapy modalities.

The efficacy of HDDPiW-jSB solution on docetaxel-induced alopecia of rats.

OBJECTIVE: Chemotherapy induced alopecia (CIA) is one of the most common side effects in cancer patients, however; it doesn't have an effective pharmacological treatment yet. In this study we aimed to research the protective effect of newly developed HDDPiW-jSB solution on docetaxel (DTX) -induced rat alopecia model. MATERIAL AND METHODS: Docetaxel (10 mg/kg/week) was administered to the 6-8 months old rats for three weeks. HDDPiW-jSB solution was applied once or twice a week for 4 weeks beginning prior to one week before DTX. Rat hair follicles were evaluated with hematoxylin-eosin and immune-histochemical staining. RESULTS: In the first stage of this study, alopecia was successfully developed by DTX (10 mg/kg/three times) application. In the second stage of the study, application of HDDPiW-jSB solution, did not change the study parameters significantly on control group. The solution improved the anagen hair follicle count and Bcl-2 levels in the skin samples of DTX-induced alopecic rat groups, especially when applied twice weekly. Additionally, level of Caspase 3 was decreased. HDDPiW-jSB solution was safe when applied on the skin. CONCLUSION: Topical HDDPiW-jSB solution could be effective and safe for the protection of DTX-induced alopecia in rat models.

HALP Score as a New Prognostic Factor for Patients with Metastatic Bladder Cancer.

OBJECTIVE: To investigate the effect of the haemoglobin, albumin, lymphocyte, and platelet (HALP) score (Haemoglobin, Albumin, Lymphocyte, Platelet count) on survival as a new prognostic factor in metastatic bladder cancer. STUDY DESIGN: Descriptive study. Place and Duration of the Study: Department of Medical Oncology, Celal Bayar University, Manisa, Turkey, and Adnan Menderes University, Aydin, Turkey, from 2010 to 2020. METHODOLOGY: The medical charts of patients with metastatic bladder cancer were reviewed retrospectively. Prognostic value of the HALP score as a marker of overall survival was examined through a receiver operating characteristic (ROC) curve analysis. RESULTS: The cut-off value for the HALP score in the ROC curve analysis was 29. The median overall survival (OS) was 19 months when the HALP score was less than 29, and the median OS was 40 months when the HALP score was 29 or greater, and this finding was statistically significant (p = 0.003). CONCLUSION: The HALP score is closely related to prognosis in metastatic bladder cancer. A high HALP score is associated with better survival outcomes. KEY WORDS: HALP score, Metastatic bladder cancer, Overall survival.

Factors Predicting Response in Breast Cancer Receiving Neoadjuvant Therapy and the Role of Ki67 Labeling Index.

OBJECTIVE: To determine the predictive value of Ki67 on pathological complete response (pCR) of breast and axilla regions in breast cancer (BC) patients receiving neoadjuvant therapy (NAT). STUDY DESIGN: Descriptive study. Place and Duration of the Study: Departments of Medical Oncology, Sirnak State Hospital, Aydin State Hospital, Manisa Celal Bayar University, and Dokuz Eylul University, from November 2010 to July 2022. METHODOLOGY: PCR and various histopathological parameters were evaluated for BC patients receiving NAT. The Youden Index method was used to find the cut-off value for the Ki67 variable according to the receiver operating characteristic (ROC) curve. This value was obtained as 77.5. Breast and axillary responses were individually evaluated to assess response to NAT. Univariate and multivariate logistic regression analysis were used to predict both breast and axillary pCR. RESULTS: A total number of 280 females receiving NAT for BC were included in the study. Multivariate analysis for breast pCR to NAT showed that Ki67 index (>77.5 vs <77.5, p=0.047) was statistically significant marker. While Ki67 index was significant for breast pCR in both univariate and multivariate analyses, the same was not observed on axillary response (p=0.387). CONCLUSION: High Ki67 level was significantly associated with breast pCR in BC patients receiving NAT, but a similar effect was not observed on axillary pCR. These findings suggest that breast and axilla tissues have a biological differences in treatment responses. KEY WORDS: Axillary response, Breast cancer, Ki67 Labeling Index, Neoadjuvant therapy, pathological complete response.

The Potential Prognostic Marker TyG Index Predicts Time to Brain Metastasis at HER2 Positive Breast Cancer.

Background: We aimed to investigate the prognostic significance of insulin resistance (IR) markers fasting triglyceride-glucose (TyG) index and triglyceride high-density lipoprotein cholesterol (TG/HDL-C) ratio in HER2-positive breast cancer (BC) patients with brain metastasis (BM). Methods: In this single-center study, 120 patients who met the criteria were included. TyG and TG/HDL-C at the time of diagnosis were computed retrospectively. For TyG and TG/HDL-C, the median values of 9.32 and 2.95 were taken as the cut-off, respectively. TyG values <9.32 and <2.95 were considered low, and TG/HDL-C values ≥9.32 and ≥2.95 were considered high. Results: The median overall survival (OS) was 47 months (95% CI: 40.54-53.45). Time to BM was 22 months (95% CI: 17.22-26.73). The median time to BM was 35 months (95% CI: 20.90-49.09) in the low TyG group and 15 months (95% CI: 8.92-21.07) in the high TyG group (p < 0.001). The time to BM was 27 months (95% CI: 20.49-33.50) in the low TG/HDL-C group and 20 months (95% CI: 16.76-23.23) in the high TG/HDL-C group (p=0.084). In the multivariate Cox regression analysis, the TyG index (HR: 20.98, 95% CI: 7.14-61.59, p < 0.001) was an independent risk factor for time to BM. Conclusion: These findings suggest that the TyG index could be used as a predictive biomarker at the time of diagnosis for risk of time BM in patients with HER2-positive BC. The TyG index can be used as a standard potential marker with prospective studies confirming these data.

Systemic Immune Inflammation Index as a Key Marker of Survival and Immune-related Adverse Events in Immune Checkpoint Inhibitor Therapy.

OBJECTIVE: To evaluate the prognostic significance of the new index designed by formulating neutrophil, lymphocyte, and platelet counts in patients with metastatic disease receiving immune checkpoint inhibitors (ICI) and its effect on the immune-related adverse events (irAEs). STUDY DESIGN: Cohort study. PLACE AND DURATION OF STUDY: Department of Medical Oncology, University of Manisa Celal Bayar, University of Aydin Adnan Menderes, and University of Ege, and Izmir Kent Hospital, Turkey, from January 2016 to April 2020. METHODOLOGY: Patients with metastatic disease receiving ICI sufficient follow-up data were included. Patients, who had received treatment for a minimum of 3 months, were evaluated for the response. Systemic immune-inflammation index (SII) was calculated as neutrophil (/L) × (lymphocyte (/L) / platelet (/L). The cut-off value was determined by examining the area under the receiver operating characteristic (ROC) curve for the SII value. The endpoints of this study included overall survival (OS) and progression-free survival (PFS). RESULTS: A total of 168, patients who received ICI in the metastatic stage, were evaluated. The OS of the patients with low SII scores was 110.8 months (95% CI, 88.2-133.5), while patients with high SII scores were 36.0 months (95% CI, 28.4-43.6) and reached statistical significance (p <0.001). The results of univariate (HR=3.376, 95% CI, 1.986-5.739, p<0.001 and multivariate (HR=2.792, 95% CI, 1.495-5.215, p=0.011) analyses were statistically significant as well. CONCLUSION: The SII score in patients with metastatic disease receiving ICI was closely related to the prognosis. Patients with a high SII score are associated with a worse prognosis, these patients develop fewer irAEs. KEY WORDS: Systemic immune inflammation index, Overall survival, Progression-free survival, Immune checkpoint inhibitor, Pembrolizumab, Nivolumab.

Atezolizumab combined with chemotherapy in the first-line treatment of extensive-stage small cell lung cancer: a real-life data of the Turkish Oncology Group.

PURPOSE: Atezolizumab has been shown to be effective and safe in randomized trial in the first-line treatment of extensive-stage small cell lung cancer (SCLC). However, there are limited real-life data on atezolizumab. In this study, we aimed to determine the real-life efficacy and safety of atezolizumab combined with chemotherapy in the first-line treatment of extensive-stage SCLC. METHODS: This trial is a retrospective multicenter study of the Turkish Oncology Group, which included extensive-stage SCLC patients who received atezolizumab combined with chemotherapy in a first-line treatment. The characteristics of the patients, treatment and response rates, and PFS and OS are presented. Factors associated with PFS and OS were analyzed by univariate and multivariate analysis. RESULTS: A total of 213 patients at the 30 oncology centers were included. The median number of chemotherapy cycle was 5 (1-8) and atezolizumab cycle was 7 (1-32). After median 11.9 months of follow-up, median PFS and OS was 6.8 months (95%CI 5.7-7.8), and 11.9 months (95%CI 11-12.7), respectively. The ORR was 61.9%. ECOG-PS (p = 0.002) and number of metastatic sites (p = 0.001) were associated with PFS and pack-year of smoking (p = 0.05), while ECOG-PS (p = 0.03) and number of metastatic sites (p = 0.001) were associated with OS. Hematological side effects were common and toxicities were manageable. CONCLUSION: This real-life data confirm the efficacy and safety of atezolizumab in combination with chemotherapy in first-line treatment of extensive-stage SCLC.