Predictive significance of inflammatory markers and mGPS in metastatic castration-resistant prostate cancer treated with abiraterone or enzalutamide.

BACKGROUND: Prostate cancer is a prevalent cancer in men worldwide, and castration-resistant prostate cancer (CRPC) is characterized by disease progression despite androgen deprivation therapy. While clinical and prognostic biomarkers have been identified in CRPC, the significance of serum inflammatory markers remains unclear. MATERIALS AND METHODS: This retrospective study included 79 CRPC patients treated with abiraterone or enzalutamide. Inflammatory markers, including the modified Glasgow prognostic score (mGPS), systemic immune-inflammation index (SII), and neutrophil-to-lymphocyte ratio (NLR), were assessed as predictive tools for treatment response. Patient data were obtained from medical charts, and statistical analyses were performed. RESULTS: The median age of the patients was 67 years, with most having a Gleason score of 8-10. The median values for NLR, PLR, and SII were 2.9, 168.5, and 713.5, respectively. The objective response rate (ORR) to abiraterone or enzalutamide therapy was 55.1%. mGPS showed a significant association with ORR, with the mGPS 0 group having the highest response rate (59.5%). Median progression-free survival (PFS) was 12.8 months, and median overall survival (OS) was 35.4 months. Palliative radiotherapy during therapy and PSA doubling time were independent prognostic factors for PFS. CONCLUSIONS: mGPS and PSA doubling time significantly impacted survival, and mGPS significantly predicted the treatment response in mCRPC, which may lead to further prospective studies.

Associations of serum uric acid levels and anthropometric parameters with non-alcoholic fatty liver disease in healthy individuals: innovative insights from a cross-sectional study.

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD is a spectrum of liver disease with a rising prevalence, ranging from simple steatosis to steatohepatitis and cirrhosis, where a significant minority face potential complications. Determining the predictive markers plays a crucial role. This study examined the relationship between serum uric acid (SUA) levels and NAFLD in healthy individuals and identified potential other predictors. MATERIAL AND METHODS: A cohort of 2162 healthy participants attending routine check-up visits between February 2021 and May 2023 were included. Participants underwent abdominal ultrasound, uric acid measurements, and anthropometric assessments by TANITA. NAFLD was graded using a "hepatic steatosis score." Statistical analysis included nonparametric tests, chi-squared tests, Fisher's exact test, ROC curve analysis, and logistic regression. RESULTS: The median age was 45 years (range:18-65). 1017 were male, and 1145 were female. Among the participants, 53.9%, 26.3%, 17.9%, and 1.9% exhibited Grade 0, 1, 2, and 3 hepatic steatosis, respectively. ROC analysis showed 80.0% sensitivity and 78.8% specificity for detecting grade 2 or higher hepatic steatosis with a cutoff value of 5.21 mg/dl of SUA (AUC = 0.82, p < 0.001, 95%CI 0.79-0.84). There were significant associations between elevated uric acid levels and NAFLD. Participants with higher body fat percentages, BMI values, and waist-to-hip ratios also demonstrated an increased prevalence of steatosis. Gender significantly influenced liver steatosis, with males exhibiting higher grades compared to females. Logistic regression analysis highlighted positive associations between NAFLD and body fat percentage, waist-to-hip ratio, and uric acid levels. Each unit increase in uric acid levels corresponded to a 2.5-fold increase in the odds of NAFLD (p < 0.001, 95% CI = 2.20-2.84). CONCLUSION: Our findings suggest a significant relationship between serum uric acid levels and NAFLD in healthy individuals. Elevated uric acid levels, in conjunction with other anthropometric parameters, may serve as potential predictive markers for NAFLD.

Impact of SPARC expression on treatment response of pembrolizumab and brain metastasis in patients with metastatic non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) often exhibits elevated Secreted Protein Acidic and Cysteine-Rich (SPARC) expression. In this study, we investigated the impact of SPARC expression on clinicopathologic features, pembrolizumab response, and prognosis in metastatic NSCLC patients. METHODS: Thirty-six patients diagnosed with metastatic NSCLC without actionable driver mutation and who received pembrolizumab with or without chemotherapy were included in this study. PD-L1 and SPARC expression were evaluated, with PD-L1 expression categorized based on tumor proportion score and SPARC staining intensity graded as 1+, 2+, and 3 +. Patients' characteristics were compared across groups, and possible predictive markers were determined by binary logistic regression analysis. RESULTS: No significant associations were found between SPARC expression and smoking status, histopathological tumor type, T and N status, and liver and bone metastasis. Higher SPARC expression was significantly linked to lower brain metastasis rates but higher CNS progression rates (p = 0.022 and p = 0.011, respectively. The objective response rate (ORR) showed a trend of being higher in the SPARC 1 + group (85.7% vs. 43.8% and 50.0% in 2 + and 3 + groups, respectively, p = 0.052. Univariate analysis did not find SPARC expression to be a significant prognostic factor for progression-free survival (PFS) (p = 0.7) and overall survival (OS) (p = 0.07).SPARC 1 + expression negatively affected the pembrolizumab response(p = 0.04,OR:0.11, 95%CI 0.01-0.92). CONCLUSIONS: Our study sheds light on a novel aspect of SPARC expression as a potential predictor of pembrolizumab response and a marker for CNS progression in metastatic NSCLC patients treated in the first-line setting.

Relationship between the change in tumour-infiltrating lymphocyte level and residual tumour after neoadjuvant chemotherapy in patients with locally advanced breast cancer.

To evaluate the tumour-infiltrating lymphocyte (TIL) rates in breast tissue before and after neoadjuvant chemotherapy (NAC) and their impact on survival, eighty-four patients with locally advanced breast cancer (LABC) were assessed. Pre- and post-NAC TIL levels were determined using biopsy and surgical specimens, respectively. The median TIL rate was significantly different before (17.5%) and after (5%) NAC. Pre- and postoperative Ki-67 index, molecular subtype, pre- and post-NAC TIL concentration, and preoperative residual-cancer-burden TIL were significantly associated with pathological complete response (pCR). Specifically, higher pre-NAC TIL levels were associated with higher pCR rates. Postoperative Ki-67 index and pCR, and postoperative Ki-67 index were significant predictors of disease-free (DFS) and overall survival, respectively. The independent prognostic factors for DFS were postoperative Ki-67 score (hazard ratio [HR]: 6.16; p = 0.012), post-NAC TIL score (HR: 0.42; P = 0.041), and pCR (HR: 0.10; P = 0.038). Our study confirms that higher pre-NAC and lower postoperative TIL levels may be surrogate factors for longer DFS, and postoperative TIL rate may predict post-NAC pCR in patients with LABC.

Prognostic factors for regorafenib treatment in patients with refractory metastatic colorectal cancer: A real-life retrospective multi-center study.

Regorafenib, an oral multikinase inhibitor, has improved survival in metastatic colorectal cancer (mCRC) patients who have progressed on standard therapies. Our study aimed to evaluate prognostic factors influencing regorafenib treatment and assess the optimal dosing regimen in a real-life setting. We retrospectively analysed 263 patients with mCRC from multiple medical oncology clinics in Turkey. Treatment responses and prognostic factors for survival were evaluated using univariate and multivariate analysis. Of the patients, 120 were male, and 143 were female; 28.9% of tumors were located in the rectum. RAS mutations were present in 3.0% of tumors, while BRAF, K-RAS, and N-RAS mutations were found in 3.0%, 29.7%, and 25.9% of tumor tissues, respectively. Dose escalation was preferred in 105 (39.9%) patients. The median treatment duration was 3.0 months, with an objective response rate (ORR) of 4.9%. Grade ≥ 3 treatment-related toxicity occurred in 133 patients, leading to discontinuation, interruption, and modification rates of 50.6%, 43.7%, and 79.0%, respectively. Median progression-free survival (PFS) and overall survival (OS) were 3.0 and 8.1 months, respectively. RAS/RAF mutation (hazard ratio [HR] 1.5, 95% confidence interval [CI] 1.1-2.3; P = 0.01), pretreatment carcinoembryonic antigen (CEA) levels (HR 1.6, 95% CI 1.1-2.3; P = 0.008), and toxicity-related treatment interruption or dose adjustment (HR 1.6, 95% CI 1.1-2.4; P = 0.01) were identified as independent prognostic factors for PFS. Dose escalation had no significant effect on PFS but was associated with improved OS (P < 0.001). Independent prognostic factors for OS were the initial TNM stage (HR 1.3, 95% CI 1.0-1.9; P = 0.04) and dose interruption/adjustment (HR 0.4, 95% CI 0.2-0.9; P = 0.03). Our findings demonstrate the efficacy and safety of regorafenib. Treatment line influences the response, with dose escalation being more favorable than adjustment or interruption, thus impacting survival.

Real-life analysis of treatment approaches and the role of inflammatory markers on survival in patients with advanced biliary tract cancer.

OBJECTIVES: Advanced-stage biliary tract cancers (BTC) are rare malignancies with poor prognosis. There are few prospective trials, but several retrospective studies regarding treatment options. In this study, we aimed to investigate the role of systemic inflammatory parameters (SIP) and other possible independent factors that may affect survival and treatment approaches and to determine the benefit of later-line treatments in these patients. METHODS: A total of 284 patients, initially diagnosed with advanced stage or progressed after curative treatment of BTC, from different oncology centers in Turkey were included in this retrospective study. The prognostic significance of clinicopathological factors, SIPs and treatment options was analyzed. RESULTS: At a median follow-up of 13 months, the median progression-free survival (PFS) was 6.1 months (95% CI:5.51-6.82), and the median overall survival (OS) time was 16.8 months (95% CI: 13.9-19.6). Treatment choice (p < .001 HR:0.70 CI95% 0.55-0.9), performance status (p < .001 HR:2.74 CI 95% 2.12-3.54) and neutrophil-to-lymphocyte ratio (NLR) (p = .02 HR:1.38 CI 95% 1.03-1.84) were independent prognostic factors for PFS. For OS, the independent prognostic indicators were determined as The Eastern Cooperative Oncology Group Performance Status (ECOG PS) (p < .001 HR:1.78 CI 95% 1.5-2.3), Systemic Immune-inflammation Index (SII) (p < .001 HR:0.51 CI95% 0.36-0.73) and stage at diagnosis (p = .002 HR:1.79 CI 95% 1.24-2.59). Furthermore, second and third line treatments significantly prolonged OS in advanced BTC (p < .001 HR:0.55 CI 95% 0.38-0.79; p = .007 HR:0.51 CI95% 0.31-0.83, respectively). CONCLUSION: SII and NLR are useful prognostic factors and may be helpful in making treatment decisions. Additionally, second and later-line treatments in advanced BTC have a significant impact on survival under real-life conditions.

Cisplatin plus paclitaxel and bevacizumab versus carboplatin plus paclitaxel and bevacizumab for the first-line treatment of metastatic or recurrent cervical cancer.

OBJECTIVE: Cisplatin-paclitaxel and bevacizumab is a frequently used treatment regimen for metastatic or recurrent cervical cancer, and carboplatin-paclitaxel and bevacizumab are also among the recommended regimens. In this study we aimed to evaluate the efficacy of these two regimens for the treatment of metastatic or recurrent cervical cancer. METHODS: Patients with metastatic or recurrent cervical cancer treated with cisplatin-paclitaxel and bevacizumab or carboplatin-paclitaxel and bevacizumab were retrospectively evaluated in this study. The clinical and demographic characteristics of patients in each group were evaluated. Median overall survival, progression-free survival, and response rates between the two groups were compared. RESULTS: A total of 250 patients were included. Overall, the numbers of patients with recurrent disease and metastatic disease were 159 and 91, respectively. The most common histologic subtype was squamous cell carcinoma (83.2%). The median duration of follow-up was 13.6 (range 0.5-86) months. The median progression-free survival was 10.5 (95% CI 9.0 to 11.8) months in the cisplatin-paclitaxel and bevacizumab group (group 1), and 10.8 (95% CI 8.6 to 13.0) months in the carboplatin-paclitaxel and bevacizumab group (group 2) (HR 1.20; 95% CI 0.88 to 1.63; p=0.25). The median overall survival was 19.1 (95% CI 13.0 to 25.1) months in group 1 and 18.3 (95% CI 15.3 to 21.3) months in group 2 (HR 1.28; 95% CI 0.91 to 1.80; p=0.15). CONCLUSIONS: There is no survival difference between cisplatin or carboplatin combined with paclitaxel and bevacizumab in metastatic or recurrent cervical cancer.

Effect of Adjuvant Chemotherapy in Stage III Cervical Cancer Patients Treated with Concurrent Chemoradiation: A Multicenter Study.

INTRODUCTION: A significant proportion of cervical cancer (CC) patients are diagnosed at a locally advanced stage. Concurrent chemoradiotherapy (CCRT) is the cornerstone of treatment for patients with locally advanced CC. However, the role of adjuvant chemotherapy (AC) after CCRT is controversial. In this study, we analyzed the efficacy of AC after CCRT in stage III CC patients. METHODS: We performed a multicenter, retrospective analysis of 139 International Federation of Gynecology and Obstetrics stage III CC patients treated with CCRT of whom 45.3% received AC. Our goal was to determine the impact of AC on survival in these patients. RESULTS: Five-year progression-free survival (PFS) was 37.5% and 16% in patients receiving CCRT with and without AC, respectively (p = 0.008). Median PFS was 30.9 months (CI 95% 14.8-46.9) and 16.6 months (CI 95% 9.3-23.9) in patients receiving CCRT with and without AC, respectively. Five-year overall survival (OS) was 78.2% and 28.4% in patients receiving CCRT with and without AC, respectively (p < 0.001). Median OS was 132.2 months (CI 95, %66.5-197.8) and 34.9 months (CI 95% 23.1-46.7) in patients receiving CCRT with and without AC, respectively. CONCLUSION: Our study suggests that AC provides OS and PFS benefit in stage III CC patients. Larger studies are needed to identify subgroups of patients who would benefit from AC.

The Role of 18F-FDG PET/CT in Predicting the Neoadjuvant Treatment Response in Patients with Locally Advanced Breast Cancer.

Purpose: Patients with locally advanced breast cancer (LABC) should be treated with neoadjuvant chemotherapy (NAC). Pathological complete response (pCR) is related to better disease-free survival (DFS). The best strategy for assessing the efficacy of NAC has not been established yet, but several studies have shown that 18F-FDG PET/CT is a potential imaging tool for assessing pCR. The aim of this study is to investigate the merits of 18F-FDG PET/CT imaging in predicting pCR in both axillary and breast tissue and to establish a threshold maximum standard uptake value (SUVmax) for predicting the response after completion of NAC. Methods: A total of 186 LABC patients, treated with an NAC regimen according to tumor subtype, were retrospectively analyzed in this study. All patients underwent 18F-FDG PET/CT imaging before and after completion of NAC. PET parameters were measured in the most FDG avid breast tissue and axillary lymph nodes. We analyzed the correlation between the tumor SUVmax of the PET/CT response and the pCR after surgery. DFS was also evaluated with respect to pCR. Results: Higher pCR rates were significantly associated with a higher tumor grade, an initial Ki-67 ≥20% (p = 0.03 and p = 0.003, respectively), a triple-negative subtype (32.9%), and a human epidermal growth factor receptor 2 (HER-2)-positive subtype (24.7%) (p < 0.001). There was a significant correlation between the pCR and a complete response in 18F-FDG PET/CT (p < 0.001). The overall sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of 18F-FDG PET/CT to determine the pCR after NAC were 100%, 72.2%, 85%, 75.2%, and 100%, respectively. We demonstrated a 1.1 cutoff SUVmax for breast tumors after NAC (OR: 3.94, 95% CI: 1.14-5.05, p = 0.004), the 18F-FDG PET/CT response to NAC (OR: 0.50, 95% CI: 0.25-0.99, p = 0.003), and the molecular subtype of breast tumors (OR: 0.58, 95% CI: 0.38-0.88, p = 0.011). Conclusion: Our results confirm that 18F-FDG PET/CT is a useful method for predicting the NAC response in LABC.

Assessment of Prognostic Factors and Adjuvant Treatment Modalities in Adult Head and Neck Soft Tissue Sarcoma Patients Treated With Upfront Surgery.

Objectives Head and neck soft tissue sarcomas (HNSTSs) are a heterogeneous group of rare tumors. Surgical resection with negative margins remains the standard primary treatment for patients with HNSTS. The role of chemotherapy (CT) and radiotherapy (RT) remains controversial. In this multicenter study, we aimed to demonstrate the real-world assessing prognostic factors and the effect of adjuvant treatment modalities in adult patients with HNSTS treated with upfront surgery. Methods We included a total of 47 patients who underwent curative-intent resection of a primary HNSTS between 2000 and 2019. Results The median follow-up was 29 months. The median age of patients was 51 years, and 66% of patients were male. The median relapse-free survival (RFS) of the study population was 31 months (range: 1.0-61.1 months), and the median overall survival (OS) was 115 months (range: 60.8-169.2 months). The univariable analysis revealed that treatment modalities showed a significant impact on RFS (p = 0.021); however, no difference was found in its impact on OS (p = 0.137). R0 resection did not showed impact on RFS (p = 0.130), but a significant association was found with OS (p = 0.004). In multivariable analysis, T stage of the tumor (hazard ratio [HR]: 3.834; 95% CI: 1.631-9.008; p = 0.002) and treatment with surgery and sequential RT and CT (HR: 0.115; 95% CI: 0.035-0.371; p < 0.001) were independent factors associated with RFS. R0 resection was independently associated with OS (HR: 4.902; 95% CI: 1.301-18.465; p = 0.019). Conclusion Our study revealed that R0 resection improved OS, and T3-4 stage of tumor was a negative independent factor for RFS in surgically resected HNSTS patients. The use of sequential CT and RT after resection was associated with a better RFS, which emphasizes the importance of multidisciplinary evaluation of the treatment of HNSTS. Randomized prospective studies are needed.