Efficacy of subsequent treatments in patients with hormone-positive advanced breast cancer who had disease progression under CDK 4/6 inhibitor therapy.

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.

Real-life experience of patients with sarcomatoid renal cell carcinoma: a multicenter retrospective study.

Sarcomatoid renal cell carcinoma (sRCC) is a rare variant of renal cell carcinoma (RCC) and is associated with a poor prognosis. We reviewed the outcomes of patients from oncology centers in Turkey. Our aim is to share our real-life experience and to contribute to the literature. The demographic and clinical features, treatment, and survival outcomes of 148 patients with sRCC were analyzed. The median age at the time of diagnosis was 58 years (range: 19-83 years). Most patients (62.8%) had clear-cell histology. Most patients were in the intermediate Memorial Sloan-Kettering Cancer Center (MSKCC) risk group (67.6%) and were stage 4 at the time of diagnosis (63.5%). The most common sites of metastasis were the lung (60.1%), lymph nodes (47.3%), and bone (35.8%). The patients received a median of two lines (range: 0-6) of treatment. The most common side effects were fatigue, hematological side effects, hypertension, and hypothyroidism. The median follow-up was 20.9 months (range: 1-162 months). The median overall survival (OS) was 30.8 months (95% confidence interval: 24.9-36.7 months). In multivariate analysis, high MSKCC scores, sarcomatoid differentiation rates >50%, having stage 4 disease, and having lung metastasis at the time of diagnosis were independent factors for poor prognosis affecting OS. No difference was observed between patients who received tyrosine kinase inhibitor (TKI) as the first or second-line treatments. Similarly, no difference between TKI and immunotherapy as the second-line treatment. In conclusion, sRCC is a rare variant of RCC with a poor prognosis and response to treatment. Larger-scale prospective studies are needed to define an optimal treatment approach for longer survival in this aggressive variant.

Clinical Features and Prognostic Factors of Metastatic Non-Clear Cell Renal Cell Carcinoma: A Multicenter Study from the Turkish Oncology Group Kidney Cancer Consortium.

INTRODUCTION: We aimed to evaluate clinical features, prognostic factors, and treatment preferences in patients with non-clear cell renal cell carcinoma (nccRCC). METHODS: Patients with metastatic nccRCC were selected from the Turkish Oncology Group Kidney Cancer Consortium (TKCC) database. Clinical features, prognostic factors, and overall survival (OS) outcomes were investigated. RESULTS: A total of 118 patients diagnosed with nccRCC were included in this study. The median age at diagnosis was 62 years (interquartile range: 56-69). Papillary (57.6%) and chromophobe tumors (12.7%) are common histologic subtypes. Sarcomatoid differentiation was present in 19.5% of all patients. When the patients were categorized according to the International Metastatic RCC Database Consortium (IMDC) risk scores, 66.9% of the patients were found to be in the intermediate or poor risk group. Approximately half of the patients (55.9%) received interferon in the first line. At the median follow-up of 53.2 months (95% confidence interval [CI]: 34.7-71.8), the median OS was 19.3 months (95% CI: 14.1-24.5). In multivariate analysis, lung metastasis (hazard ratio [HR]:2.22, 95% CI: 1.23-3.99) and IMDC risk score (HR: 2.35, 95% CI: 1.01-5.44 for intermediate risk; HR: 8.86, 95% CI: 3.47-22.61 for poor risk) were found to be independent prognostic factors. CONCLUSION: In this study, survival outcomes are consistent with previous studies. The IMDC risk score and lung metastasis are the independent prognostic factors for OS. This is an area that needs research to better treat this group of patients and create new treatment options.

Nivolumab in metastatic renal cell carcinoma: results from the Turkish Oncology Group Kidney Cancer Consortium database.

Aim: The authors present real-world data on the efficacy and safety of nivolumab in patients with metastatic renal cell carcinoma (mRCC). Methods: The Turkish Oncology Group Kidney Cancer Consortium (TKCC) database includes patients with mRCC from 13 cancer centers in Turkey. Patients with mRCC treated with nivolumab in the second line and beyond were extracted from the TKCC database. Results: A total of 173 patients were included. The rates of patients treated with nivolumab in the second, third, fourth and fifth lines were 47.4%, 32.4%, 14.5% and 5.7%, respectively. The median overall survival and progression-free survival were 24.2 months and 9.6 months, respectively. Nivolumab was discontinued owing to adverse events in 11 (6.4%) patients. Conclusion: Nivolumab was effective in patients with mRCC and no new safety signal was observed.

Lay abstract Nivolumab is an immune checkpoint inhibitor (ICI) that blocks the communication between T cells and cancer cells and instead activates T cells to fight against cancer. Metastatic renal cell carcinoma (mRCC) is one of the most susceptible tumors to ICIs. The Checkmate 025 trial showed the efficacy of nivolumab in patients with previously treated mRCC. In this real-world study, 173 patients with mRCC were treated with nivolumab in the second line and beyond. Nivolumab was effective in the real-world setting without additional safety concerns.

Trimester-specific reference intervals of thyroid function tests in Turkish pregnants.

Physiological changes in hormone levels occur in thyroid gland during pregnancy. Screening of the thyroid hormone levels and determining trimester-specific reference intervals in pregnancy are important. Guidelines recommend the use of trimester-specific reference ranges for each country. The aim of this study is to determine trimester-specific thyroid function reference intervals for pregnancy in Turkish population. In total, 5000 patients were screened out of which 1258 patients have all of fT3, fT4 and TSH levels measured, were included in the study. Patients were grouped as follows: 482 women were in first trimester, 361 women were in second trimester, and 415 women were in third trimester. All analyses were performed by means of chemiluminescence methods (Liaison®; DiaSorin S.p.A., Saluggia, Italy). The TSH reference intervals were 0.005-3.65, 0.01-3.63, and 0.2-3.46 mIU/L at the first, the second, and the third trimesters of pregnancy, respectively. The fT4 reference intervals were 0.72-1.79, 0.71-1.26, and 0.65-1.12 ng/dL at the first, the second, and the third trimesters, respectively. The fT3 reference intervals were 2.45-4.03, 2.37-3.85, and 2.31-3.77 ng/dL at the first, the second, and the third trimesters, respectively. It is crucial to determine population- and gestational-specific reference intervals for trustworthy treatment of pregnants.

The relationship between prognostic nutritional index and treatment response in patients with metastatic renal cell cancer.

INTRODUCTION AND AIM: To investigate the effect of the prognostic nutritional index on treatment response and survival in patients with metastatic renal cell cancer. METHODS: We retrospectively analyzed the treatment modalities; the demographic, clinical and pathological features of 396 patients with RCC and prognostic nutritional index. Based on the median value, patients were grouped as having low and high prognostic nutritional index values. Kaplan-Meier method was used for survival analysis, and Cox-regression analysis was used for multivariate analysis. RESULTS: The median overall survival was 39 months (95% CI 26.1-51.8), 28 months (95% CI 17.9-38) and 7 months (95% CI 4.7-9.2) in patients with favorable, intermediate and poor International Metastatic Renal Cell Carcinoma Database Consortium risk group, respectively. The difference between the groups was statistically significant (p < 0001). Overall survival was 11 months (95% CI 7.5-14.5) in the low-prognostic nutritional index (prognostic nutritional index ≤38.5) group, and 41 months (95% CI 30.5-51.4) in the high prognostic nutritional index (prognostic nutritional index >38.5) group (p < 0.001). In Cox regression analysis, Eastern Cooperative Oncology Group performance score (HR: 2.5), time to systemic treatment (HR: 1.7) and prognostic nutritional index (HR: 1.8) were associated with overall survival. CONCLUSION: In patients with renal cell cancer, prognostic nutritional index is closely related to survival and has prognostic significance.

Neutrophil-lymphocyte ratio as a prognostic factor for survival in patients with advanced renal cell carcinoma (Turkish Oncology Group Study).

BACKGROUND: To describe the prognostic value of neutrophil-lymphocyte ratio and its effect on survival in in patients with advanced renal cell carcinoma. METHODS: We retrospectively analyzed 331 patients. The cut-off value of neutrophil-lymphocyte ratio was specified as "3" which is mostly close-and also clinically easily applicable-to the median neutrophil-lymphocyte ratio level of our study group. High group is identified as neutrophil-lymphocyte ratio >3 (n = 160) and low group is identified as neutrophil-lymphocyte ratio ≤3 (n = 163). RESULTS: A total of 331 (with 211 male and 120 female) patients were enrolled to study. The median age of the patients was 58. The International Metastatic RCC Database Consortium risk score is calculated for the 72.8% (n = 241) of the study group and among these patients, favorable, intermediate, and poor risk rates were 22, 45.2, and 32.8%. The total usage of tyrosine kinase inhibitors reached 78% of the patients. The median overall survival was 32 months versus 11 months in the neutrophil-lymphocyte ratio low and high groups, respectively (HR: 0.49 (95% CI 0.37-0.65), p < 0.001). CONCLUSION: In conclusion, the pre-treatment value of elevated neutrophil-lymphocyte ratio might be a predictor of poor overall survival in advanced renal cell carcinoma patients.

The neutrophil-lymphocyte ratio and its relationship with insulin resistance in obesity

Background/aim: In this study, our aim was to investigate the neutrophil/lymphocyte (N/L) ratio, variations in leukocytes and leukocyte subtypes, and the relationship between N/L ratio and insulin resistance (IR) in obesity. Materials and methods: Ninety-six patients and 40 healthy controls were included in this study. Patients' blood glucose levels, insulin levels, and hemogram parameters upon 8 h of fasting were determined. Body mass index (BMI) and Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) values were calculated. Results: Neutrophil numbers were found to be higher among obese patients with IR than among non-IR obese patients. The N/L ratio was, moreover, found to be higher among obese patients with IR when compared to non-IR obese patients. A positive correlation was found between insulin resistance and both neutrophil and WBC counts. Positive correlations were also found between insulin levels and the N/L ratio, WBC counts, and neutrophil counts Conclusion: In our study, leukocyte numbers and subtypes were determined to be higher among obese individuals than among healthy individuals. The N/L ratio was increased significantly only among obese patients with IR. Further studies are needed in order to better demonstrate the relationship between the N/L ratio and IR/inflammation.

Renal function improves with the treatment of hypothyroidism.

BACKGROUND: It has been known that thyroid hormones may affect renal function. In this study, we aimed to investigate the effect of levothyroxine replacement on renal function in hypothyroid patients before and after treatment. METHODS: We retrospectively investigated free T3 (fT3), free T4 (fT4), TSH, creatinine, and eGFR measurements during both hypothyroid and euthyroid states of hypothyroid patients. The eGFR was calculated using the simplified Modification of Diet in Renal Disease formula. RESULTS: fT3, fT4, and eGFR measurements increased, meanwhile creatinine and TSH levels decreased significantly after euthyroidism was achieved with levothyroxine treatment (p < 0.0001 for all). The correlation analyses revealed that ∆creatinine and ∆TSH levels were significantly correlated before and after levothyroxine treatment (r: 0.288, p < 0.0001). ∆eGFR and ∆TSH levels were significantly correlated before and after LT4 treatment (r: -0.272, p < 0.0001). CONCLUSION: In this study, we evaluated creatinine and eGFR levels in patients with hypothyroidism and found out that renal function improved in most patients after euthyroidism was achieved. In some patients, above-normal creatinine levels completely returned to normal once the patients became euthyroid.

Efficacy of Systemic Treatments in Patients With Metastatic Lung Invasive Mucinous Adenocarcinoma.

BACKGROUND: Invasive mucinous adenocarcinoma (IMA) is a rare histological subtype of lung invasive adenocarcinoma with unique clinical, radiological, histopathological, and genomic characteristics. There have been limited studies on the effectiveness of systemic therapy for lung IMA, with conflicting results reported. METHODS: We retrospectively investigated the medical records of patients diagnosed with lung IMA. Patients who were ≥ 18 years of age and received at least 1 course of treatment for metastatic or locally advanced inoperable disease were included in the study. Archive records of 113 patients diagnosed with IMA were screened for the study. RESULTS: A total of 41 patients with lung IMA were included. The targetable mutation rate was 20.6% (in 6 of 29 patients). Most patients (83.1%) had received platinum-based chemotherapy as a first-line treatment. The objective response rate (ORR) was 25.7%, and median progression-free survival (PFS) and overall survival (OS) were 8.1 months (95% CI, 5.02-11.2) and 17.5 months (95% CI, 11.7-23.3 months), respectively, in the patients who received chemotherapy. The median PFS and ORR were 20.6 (95% CI, 18.9-66.5) and 66.6%, respectively, in epidermal growth factor receptor (EGFR) mutation-positive patients (n = 3) with relevant targeted therapy. Only 1 patient used oxaliplatin and capecitabine combination (XELOX) as chemotherapy in the second-line treatment and achieved a partial response (PR) at 7.2 months. CONCLUSION: Platinum-based chemotherapies moderately enhance IMA patients' survival rates. Anti-EGFR-targeted drugs are seen as potentially effective in patients with EGFR driver mutation positive. Large, prospective studies are needed to confirm our findings.

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 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.

External Validation of a Novel Risk Model in Patients With Favorable Risk Renal Cell Carcinoma Defined by International Metastatic Renal Cell Carcinoma Database Consortium (IMDC): Results From the Turkish Oncology Group Kidney Cancer Consortium (TKCC) Database.

BACKGROUND: A novel prognostic model was recommended for patients with metastatic RCC (mRCC) by the International mRCC Database Consortium (IMDC). In this study, we aimed to externally validate a novel risk model for the IMDC-favorable risk group in patients with mRCC. METHODS: The Turkish Oncology Group Kidney Cancer Consortium (TKCC) is a multicenter registry that includes 13 cancer centers in Turkey. As described by Schmidt et al., 3 parameters (ie, time from diagnosis to systemic therapy <3 vs. ≥3 years, Karnofsky Performance Status [KPS] 80 vs. >80, and the presence of brain, liver, or bone metastasis) were used to divide the IMDC favorable risk group into 2 new categories: very favorable and favorable risk groups. The primary endpoint was overall survival (OS). Time to treatment failure (TTF) and objective response rate (ORR) in the very favorable and favorable risk groups were the secondary endpoints. RESULTS: A total of 545 patients with mRCC from all IMDC risk groups and 112 patients from the favorable risk group were included in this study. According to the novel classification model, 44 (39.3%) and 68 (60.7%) patients with former favorable risk were categorized into very favorable and favorable risk groups, respectively. The median OS (55.8 months vs. 34.2 months, P = .025) and TTF (25.5 months vs. 15.5 months, P = .010) were longer in the very favorable risk group than in the favorable risk group. The concordance index of the new IMDC model in all patients was 0.65 for OS. Despite the higher ORR in the very favorable risk group than in the favorable risk group, the difference between the groups was not statistically significant (52.4% vs. 44.7, P = .573). CONCLUSIONS: This was the first study to externally validate the novel IMDC risk model presented in the American Society of Clinical Oncology Genitourinary Cancers Symposium 2021.

Ideal Lymph Node Number for Ovarian Malignancies.

OBJECTIVE: Although there are studies in which the ideal number of lymph nodes for early-stage ovarian cancer is specified, no study has been found on the number of lymph nodes that should ideally be removed by systematic lymph node dissection, including advanced-stage patients. The present study was aimed to retrospectively investigate the number of lymph nodes that need to be removed to detect lymph node positivity and the effect of this number on prognosis. METHODOLOGY: A total of 155 patients over the age of 18 who were diagnosed with ovarian cancer without secondary malignancy and who underwent surgical lymph node dissection were included in the study between 2015 and 2020. RESULTS: A total of 155 patients underwent lymphadenectomy and the median number of removed lymph nodes was 24. Lymph node positivity was detected in 72 (46.4%) of these patients, while the median number of positive lymph nodes was 4 in the lymph node-positive group. A statistically significant positive correlation was found between the number of lymph nodes removed and the median overall survival (OS) (r = 0.546, p<0.001). At the same time, when the number of 24 lymph nodes, which is the median number of lymph nodes removed and the value found to detect lymph node positivity in the receiver operating characteristic (ROC) curve, is taken as cut off; mean OS was found to be statistically significantly higher in the group with adequate lymph node dissection compared to the group with insufficient lymph node dissection (46.46±35.22 vs 22.33±21.43; p < 0.001, respectively). CONCLUSION: it was shown that more than 24 lymph nodes are required for adequate lymph node dissection in the patients included in the study, and thus it can contribute positively to the prognosis. With the support of more comprehensive and prospective studies conducted on this subject to this study, clearer data will emerge about the number of lymph nodes that should be removed in an ideal surgery.

High Neutrophil-Lymphocyte Ratio, Platelet-Lymphocyte Ratio and Low Lymphocyte Levels Are Correlated With Worse Pathological Complete Response Rates.

OBJECTIVE: To investigate the effect of hemogram parameters on predicting pathological complete response (pCR) in locally advanced rectal cancer. METHODOLOGY: A total of 227 patients with rectal cancer treated with neoadjuvant concurrent chemoradiotherapy (CRT) were retrospectively analyzed. All patients were divided into two subgroups as high or low hemogram parameters according to the cut-off value obtained using the receiver operating characteristic (ROC) curve. RESULTS: In patients with low neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) levels, pCR rate was statistically significantly higher than the group with high NLR and PLR levels (for NLR: 39.77% vs. 5.34%; p<0.001, for PLR: 32.38% vs 7.01%; p<0.001 respectively). In addition, the pCR rate was significantly better in patients with high lymphocyte levels compared to the group with low lymphocyte levels (33.33% vs. 7.5%; p<0.001, respectively). According to the multivariate logistic regression analysis result, NLR and PLR levels were considered as independent predictors to predict pathological complete response [p<0.001, HR: 0.128 (95% CI=0.051 - 0.322) for NLR; p=0.017, HR: 0.332 (95% CI=0.134 - 0.821) for PLR, respectively]. CONCLUSION: Our study showed that high NLR, PLR, and low lymphocyte levels were correlated with worse pCR rates. In addition to that, NLR and PLR emerged as independent predictive markers.

Platelet-to-Lymphocyte Ratio as an Indicator to Predict Decreased Carbon Monoxide Diffusion of the Lung in Patients with Testicular Cancer.

OBJECTIVE: To investigate whether the use of diffusing capacity of the lungs for carbon monoxide (DLCO) and neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) could be used to predict bleomycin-induced pulmonary toxicity in patients with testicular cancer (TCa). STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Ankara Oncology Training and Research Hospital, Turkey, between 2017 and 2020. METHODOLOGY: Data of 40 patients with TCa, who were followed at cancer centre from 2017-2020 and received 3-4 cycles of BEP protocol were retrospectively screened and included who met the criteria for inclusion in the study. All patients with TCa, who were older than 18 years of age and had no secondary malignancy and comorbidity, were included in this study. RESULTS: A statistically significant negative correlation was found between DLCO change and NLR, PLR (r:-0.558, p:0.002 for NLR; r:-0.462 p:0.012 for PLR). A statistically significant positive correlation was found between DLCO change and lymphocyte level (r:0.436, p:0.018). The NLR and PLR were statistically higher in the group with a decrease of ≥10% in DLCO compared to the group with no decrease or a decrease of ≤10% in DLCO (for NLR; 3.03 ± 1.45 and 1.68 ± 0.73, respectively, p = 0.005; for PLR 187.72 ± 66.90 and 124.72 ± 47.99, respectively, p = 0.008). Multivariate regression analysis showed a statistically significant relationship between PLR increase and a decrease of ≥10% in DLCO. CONCLUSION: PLR and LDH could be used as independent predictive biomarkers for DLCO decline which is used to identify bleomycin-induced pulmonary toxicity. Key Words: Bleomycin, Markers of inflammation, Platelet-to-lymphocyte ratio (PLR), Pulmonary diffusing capacity, Testicular cancer.

Clinicopathological features of non-carcinoid malignant epithelial appendix tumors and risk factors for recurrence, single-center experience.

Background: Non-carcinoid appendix epithelial tumors are rare. These tumors include low-grade and high-grade mucinous neoplasm also adenocarcinomas. We aimed to investigate the clinicopathological features, treatment, and risk factors of recurrence. Methods: Patients diagnosed between 2008 and 2019 were retrospectively analyzed. Categorical variables were expressed as percentages and compared using the Chi-square test or Fisher's exact tests. Overall survival and Disease-free survival of the groups were calculated by the Kaplan-Meier method, and the log-rank test was used to compare the survival rates. Results: A total of 35 patients were included in the study. Of the patients, 19 (54%) were women and the median diagnosis age of patients was 50.4 years (19-76). As for pathological types, a total of 14 (40%) patients were mucinous adenocarcinoma and 14 (40%) patients were Low-Grade Mucinous Neoplasm (LGMN). Lymph node excision and lymph node involvement were 23 (65%) and 9 (25%) patients respectively. The majority of patients were stage 4 (27, 79%) and 25 (71%) of these patients had peritoneal metastasis. A total of 48.6% patients had been treated with cytoreductive surgery and hyper-thermic intraperitoneal chemotherapy. Median Peritoneal cancer index value was 12 (2-36). The median follow-up time was 20 (1-142) months. Recurrence developed in 12 (34%) of patients. When risk factors for recurrence are considered, there was a statistically significant difference in appendix tumors with high-grade, adenocarcinoma pathology, ones with peritoneal cancer index ≥12 and not having pseudomyxoma peritonei. Median disease-free survival was 18 (13-22, 95% CI) months. Median overall survival could not be reached while the 3-year survival rate was 79%. Conclusion: The risk of recurrence is higher in high-grade appendix tumors, having peritoneal cancer index ≥ 12, not having pseudomyxoma peritonei and adenocarcinoma pathology. High-grade appendix adenocarcinoma patients should be followed closely for recurrence.

The relationship between pan-immune-inflammation value and survival outcomes in patients with metastatic renal cell carcinoma treated with nivolumab in the second line and beyond: a Turkish oncology group kidney cancer consortium (TKCC) study.

BACKGROUND: Pan-immune-inflammation value (PIV) is an easily accessible immune marker based on peripheral blood to estimate prognosis in patients with cancer. This study evaluates the prognostic value of PIV in patients with metastatic renal cell carcinoma (mRCC) treated with nivolumab. METHODS: In this retrospective cohort study, patients with mRCC treated with nivolumab in the second line and beyond were selected from the Turkish Oncology Group Kidney Cancer Consortium (TKCC) database. PIV was calculated using the following formula: neutrophil (103/mm3) x monocyte (103/mm3) x platelet (103/mm3)/lymphocyte (103/mm3). RESULTS: A total of 152 patients with mRCC were included in this study. According to cut-off value for PIV, 77 (50.7%) and 75 (49.3%) patients fell into PIV-low ([Formula: see text] 372) and PIV-high (> 372) groups, respectively. In multivariate analysis, PIV-high (HR: 1.64, 95% CI 1.04-2.58, p = 0.033 for overall survival (OS); HR: 1.55, 95% CI 1.02-2.38, p = 0.042 for progression-free survival (PFS)) was independent risk factor for OS and PFS after adjusting for confounding variables, such as performance score, the International mRCC Database Consortium (IMDC) risk score, and liver metastasis. CONCLUSION: This study established that pre-treatment PIV might be a prognostic biomarker in patients with mRCC treated with nivolumab in the second line and beyond.

The relationship between systemic immune inflammation index and survival in patients with metastatic renal cell carcinomatreated withtyrosine kinase inhibitors.

This study aims to investigate the prognostic value of the systemic immune-inflammation index (SII)and its impact on survival in patients with metastatic renal cell carcinoma (mRCC). A total of 706patients with mRCC treated with tyrosine kinase inhibitors (TKIs)between January 2007 and June 2020 (i.e., sunitinib, pazopanib) were included in this study. SII was calculated in 621 patients with the following formula:[neutrophil (cellsx109/L) x platelet (cellsx109/L)] / lymphocyte (cellsx109/L).All patients were classified into SII-high and SII-low groups based on the cut-off value of SII at 756, which was the median SII level of our study group. The minimal follow-up duration was 10 months in all cohorts. The median age of patients was 60 (interquartile range (IQR):53-67) years. Three out of four patients were male. The majority of patients (85.7%) had clear cell histology, and sarcomatoid differentiation was observed in 16.9% of all patients. There were 311 and 310 patients in the SII-low and SII-high groups, respectively. In general, baseline characteristics were similar in each group. However, the rate of patients treated with sunitinib (63.3% vs. 49.0%, p < 0.001) and those who underwent nephrectomy (83.6% vs. 64.2%, p < 0.001) was higher in the SII-low group than in the SII-high group. On the other hand, patients with the IMDC poorrisk (31.6% vs. 8.0%, p < 0.001), those with bone (51.8% vs. 32.2%, p < 0.001) or central nervous system (12.9% vs. 5.8%, p = 0.026) metastasis, and those with Eastern Cooperative Oncology Group(ECOG) 2-4 performance score (28.1% vs.17.7%, p = 0.002) were more common in the SII-high group than in the SII-low group. The median overall survival (OS) was longer in the SII-low group than in the SII-high group (34.6 months vs. 14.5 months, p < 0.001). Similarly, the median progression-free survival (PFS) was longer in the SII-low group than in the SII-high group (18.0 months vs. 7.7 months, p < 0.001).In multivariableanalysis, SII was an independent prognostic factor for OS (hazard ratio (HR):1.39, 95% confidence interval (CI):1.05-1.85, p = 0.01) and PFS (HR:1.60, 95% CI:1.24-2.05, p < 0.001).Pre-treatment level of high SII might be considered a predictor of poor prognosisin patients with mRCC treated with TKIs.