Efficacy of everolimus plus hormonal treatment after cyclin-dependent kinase inhibitor; real-life experience, A TOG study.

PURPOSE: In advanced breast cancer, endocrine therapy is preferred in the absence of visceral crisis. Cyclin-dependent kinase inhibitors (CDKi) are the gold standards. The selection of subsequent treatments after CDKi treatment is still controversial, and the efficacy of everolimus (EVE) combinations is unknown. In this study, we aimed to investigate the efficacy of EVE after CDKi administration in real-life experiences. METHOD: The study received data from 208 patients from 26 cancer centers. Demographic and histologic features, diagnosis, progression, last visit dates, and toxicities were recorded. This study was a retrospective case series. RESULTS: One hundred and seven patients received palbociclib, while 101 patients received ribociclib as a CDKi. The overall response and disease control rates of EVE combinations were 60% and 88%, respectively. In univariate analysis, the absence of liver metastasis, age > 40 years, better type of response, and immediate treatment after CDKi were related to increased progression-free survival. Liver metastasis and response type were significantly associated with overall survival. In the multivariate analysis, response remained significant in terms of progression-free survival, while response type, liver metastatic disease, and hematologic toxicity were prognostic in terms of overall survival. CONCLUSION: This study provides evidence of the benefits of EVE combinations after CDKi treatment. EVE combinations may be more appropriate for patients with non-liver metastasis, and the first treatment response shows the benefit of treatment. In addition, immediate treatment after CDKi treatment is more beneficial than later lines of treatment.

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.

Geriatric nutritional risk index and controller nutritional status score before metastatic first-line chemotherapy predict survival in patients over 70 years of age with metastatic bladder cancer.

Introduction: Several prognostic factors have been identified in patients with metastatic bladder cancer (BC). As it is known, older adult patients are prone to nutritional deficiency. The knowledge about nutrition and impact on survival in older patients with metastatic bladder cancer is missing. It is necessary to specifically examine this population. Because timely interventions can make a positive impact on this patients population. This retrospective study aimed to evaluate the prognostic effect of the Geriatric Nutritional Risk Index (GNRI), Controller Nutritional Status (CONUT) score and Prognostic Nutritional Index (PNI) before first-line chemotherapy in the metastatic stage in patients with metastatic bladder cancer over 70. Participants and methods: Patients over 70 with pathologically confirmed denovo metastatic or recurrent metastatic bladder cancer were included in the study. Patients with infections diagnosed at the time of diagnosis, autoimmune diseases or history of steroid use were excluded. Since our population consists of a specific age group with a specific cancer, we found a new cut-off value by performing ROC analysis to ensure optimal sensitivity and specificity in terms of progression. Low GNRI value was related with poor nutritional status. Low PNI value was related with poor nutritional status and high CONUT score was related with poor nutritional status. Factors predicting overall survival (OS) and Progression-Free Survival (PFS) were assessed using both univariate and multivariate Cox proportional hazards analyses. Results: 106 patients were included in the study and the average age was 75.5 years. In the GNRI-Low group, PFS was significantly shorter than that in the GNRI-High group [HR (95% CI) = 57.1 (12.8-255.5), (p < 0.001)]. Among those with a low-CONUT score, PFS was found to be longer than that in the high-CONUT group [HR (95% CI) = 1.7 (1.0-3.0), (p = 0.039)]. The median PFS of the PNI-Low group wasn't significantly shorter than that of the PNI-High group [HR (95% CI) = 1.8 (0.5-6.2), (p = 0.359)]. Conclusion: Our study suggests that the GNRI and CONUT scores are useful for predicting survival in patients over 70 years of age with BC.

Survival outcomes according to the tumor location and prognostic factor in metastatic rectal cancer: a multicenter retrospective cohort study.

Background & aims: Prognostic factors of metastatic rectal cancer are not well known. We aim to determine prognostic factors affecting survival for metastatic rectal cancer patients and also to investigate the effect of tumor localization on overall survival. Methods: Metastatic rectal cancer patients who received treatment in 5 different centers between 2012 and 2022 were included. Prognostic factors for survival were evaluated using univariate and multivariate analysis. The statistical methods included Pearson's chi-square test, Fisher exact test, Log-rank test, and Cox regression model. Results: A total of 283 patients with metastatic rectal cancer were included in the study. The median OS was not significantly different among the three groups (upper rectum 30.1 months, middle rectum 28.3 months, and low rectum cancer 24.8 months; log-rank p = 0.25). In univariate analysis, Grade 3, ECOG performance status 2, the presence of multiple metastatic sites, the presence of KRAS mutation, the presence of liver metastases, the presence of nonregional lymph node metastases, and the presence of bone metastases were significant predictors of poor survival. In multivariate analysis, Grade 3, ECOG performance status 2, and the presence of multiple metastatic sites were determined as indicators of worse prognosis. Conclusion: Our findings, primary tumor location did not affect survival in metastatic rectal cancer. The most important factors affecting survival were multiple metastatic sites, tumor grade, and ECOG performance status.

Efficacy and safety of G-CSF prophylaxis in patients with extensive-stage small cell lung cancer receiving chemoimmunotherapy.

OBJECTIVES: We aimed to evaluate the efficacy and safety of granulocyte-colony stimulating factor (G-CSF) prophylaxis during chemoimmunotherapy with carboplatin plus etoposide and atezolizumab in extensive-stage small cell lung cancer (ES-SCLC). METHODS: This retrospective, multicenter study enrolled ES-SCLC patients receiving carboplatin plus etoposide and atezolizumab, categorized into G-CSF and non-G-CSF groups. Demographic and disease-related data were collected. Response rates, progression-free survival (PFS), overall survival (OS), and toxicity were analyzed. RESULTS: Of 119 patients (median age: 63 years), the overall response rate (ORR) and disease control rate (DCR) were 72.3% and 81.5%, respectively. In the G-CSF group, the ORR was 76.4% compared to 60.0% in the non-G-CSF group (p = 0.33), and the DCR was 85.4% versus 70.0%, respectively (p = 0.46). Median PFS was 8.3 months (95% CI, 6.8-9.8) in the G-CSF group and 6.8 months (95% CI, 6.2-7.5) in the non-G-CSF group (p = 0.24). Median OS was 13.8 months (95% CI, 9.6-18.1) for the G-CSF group and 10.6 months (95% CI, 7.9-13.3) for the non-G-CSF group (p = 0.47). Grade 3 ≥ adverse events were similar between groups (49.4% vs. 33.3%, respectively, p = 0.12). CONCLUSION: G-CSF prophylaxis can be safely used in ES-SCLC patients undergoing carboplatin plus etoposide and atezolizumab regimen without significantly altering efficacy or increasing toxicity.

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.

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.

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.

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.