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.

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.

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.

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.

Crizotinib efficacy and safety in patients with advanced NSCLC harboring MET alterations: A real-life data of Turkish Oncology Group.

Crizotinib is a multikinase inhibitor, effective in non-small cell lung cancer (NSCLC) harboring mesenchymal-epidermal transition (MET) alterations. Although small prospective studies showed efficacy and safety of crizotinib in NSCLC with MET alterations, there is limited real-life data. Aim of this study is to investigate real-life efficacy and safety of crizotinib in patients with advanced NSCLC harboring MET alterations. This was a retrospective, multicenter (17 centers) study of Turkish Oncology Group. Patients' demographic, histological data, treatment, response rates, survival outcomes, and toxicity data were collected. Outcomes were presented for the study population and compared between MET alteration types. Total of 62 patients were included with a median age of 58.5 (range, 26-78). Major histological type was adenocarcinoma, and 3 patients (4.8%) had sarcomatoid component. The most common MET analyzing method was next generation sequencing (90.3%). MET amplification and mutation frequencies were 53.2% (n = 33) and 46.8% (n = 29), respectively. Overall response rate and disease control rate were 56.5% and 74.2% in whole study population, respectively. Median progression free survival (PFS) was 7.2 months (95% confidence interval [CI]: 3.8-10.5), and median overall survival (OS) was 18.7 months (95% CI: 13.7-23.7), regardless of treatment line. Median PFS was 6.1 months (95% CI: 5.6-6.4) for patients with MET amplification, whereas 14.3 months (95% CI: 6.7-21.7) for patients with MET mutation (P = .217). Median PFS was significantly longer in patients who have never smoked (P = .040), have good performance score (P < .001), and responded to the treatment (P < .001). OS was significantly longer in patients with MET mutation (25.6 months, 95% CI: 15.9-35.3) compared to the patients with MET amplification (11.0 months; 95% CI: 5.2-16.8) (P = .049). In never-smokers, median OS was longer than smoker patients (25.6 months [95% CI: 11.8-39.3] vs 16.5 months [95% CI: 9.3-23.6]; P = .049). The most common adverse effects were fatigue (50%), peripheral edema (21%), nausea (29%) and diarrhea (19.4%). Grade 3 or 4 adverse effects were observed in 6.5% of the patients. This real-life data confirms efficacy and safety of crizotinib in the treatment of advanced NSCLC harboring MET alteration.

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.

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.

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.

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.

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.

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.

Evaluation of factors predicting pathologic complete response in locally advanced HER2 positive breast cancer treated with neoadjuvant pertuzumab, trastuzumab and chemotherapy; Real life data.

PURPOSE: Recently, neoadjuvant treatment approach has gained importance in locally advanced HER-2 positive breast cancer. Adding pertuzumab increases pathological complete response (pCR). In this study, we aimed to examine the clinicopathologic features that predict the pCR in patients receiving neoadjuvant pertuzumab, trastuzumab, and chemotherapy in locally advanced HER2 positive breast cancer. METHODS: Locally advanced HER2 positive breast cancer patients who were followed up in 4 different oncology centers and received 4 cycles of pertuzumab, trastuzumab and taxane were retrospectively evaluated. A total of 58 (92%) patients received anthracycline chemotherapy before combination of dual her-2 blockade and taxanes. Fisher's and chi-square tests were used for nominal variables and numeric data analyses. RESULTS: A total of 63 female patients were included in the study. Their median age was 46 years (21-75) and 40 (63.5%) patients were premenopausal. Median tumor size was 25 mm (2-70) and there were 22 (34.9%) patients with Stage 3a. pCR was 66% and 75% in the whole group and in the hormone negative group, respectively. Statistically significant increase was found in pCR in patients with grade 3 tumors and cerbB2 with 3+ immunohistochemical staining. No relationship was found between pCR and age at diagnosis, menopausal status, tumor infiltrating lymphocyte, dose-dense anthracycline, Ki67≥40, body mass index (BMI) ≥ 30 kg/m2 and accompanying DCIS. CONCLUSION: Four cycles of pertuzumab, trastuzumab and taxane after neoadjuvant anthracycline for locally advanced HER2 breast cancer are associated with increased pCR in patients with grade 3 tumors and high cerbB2 expression.

Clinical Outcomes and Prognostic Factors in HER-2 Positive Breast Cancer with Brain Metastasis: A Single-centre Experience.

OBJECTIVE:  To determine the characteristics and prognosis of brain metastasised HER-2 positive breast cancer (BC) patients. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Ankara Oncology Training and Research Hospital, Turkey between 2000 and 2019. METHODOLOGY: HER-2 positive BC patients were analysed retrospectively and 105 patients were included in the study. Age 18 years and over, HER-2 positive BC, with BM (brain metastases) were the inclusion criteria. Patients with secondary malignancies, those with missing data, and irregular follow-up were excluded from the study. The age, type of treatment, Eastern Cooperative Oncology Group Performance Status (ECOG PS) score, BM date, and the last contact date of the patients were obtained from the hospital records. The Kaplan-Meier method was used to determine the time to BM and OS. Independent factors affecting OS and time to BM were determined using the Cox regression model. RESULTS: Patients with ECOG PS score of 0-1 at the time of the BM had 19 months median overall survival (OS), while patients with ECOG PS score of 2 had 8 months (p <0.01). Median OS after BM was 32 and 14 months for patients with one BM and patients with multiple BM, respectively (p <0.01). Multivariate cox regression analyses revealed that time to progression of BM was shorter in patients with high-grade tumors compared to patients with low-grade tumors (p= 0.048), and in patients with de-novo metastasis compared to patients without de-novo metastasis (p= 0.003). Conclusion: Tumor grade and de-novo metastasis (extracranial metastasis at the time of diagnosis) are independent predictive factors that may cause the earlier occurrence of BM and affect mortality in BC patients. Key Words: Brain metastasis, Breast cancer, HER-2 positive, Metastasis.

CROSS or FLOT in Distal Esophageal and Gastroesophageal Cancer.

OBJECTIVE: To compare the chemoradiotherapy for esophageal cancer followed by surgery study (CROSS) and continuous infusion 5-FU, leucovorin, oxaliplatin, and docetaxel (FLOT) protocols administered in distal esophageal and gastroesophageal junction (GEJ) tumors in terms of effectiveness and toxicity. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Ankara Oncology Training and Research Hospital, Turkey between 2015 and 2020. METHODOLOGY: Patients diagnosed with distal esophageal and GEJ squamous cell carcinoma (SCC) or adenocarcinoma  (ADC), older than 18 years of age, in localised or locally advanced stage were included. Metastatic stages  were excluded. Kaplan-Meier was used for survival analysis, log-rank test was performed for comparisons between groups. RESULTS: A total of 25 patients (44.6%) were treated with CROSS protocol (15 distal esophageal and 10 GEJ tumor), 31 patients (55.4%) with GEJ tumors were treated with the FLOT regimen. Eight of the patients who were administered the CROSS protocol before the operation demonstrated complete pathologicial response, no patients in the FLOT group had complete response to the treatment. In patients with GEJ tumors and ADC histopathology, CROSS and FLOT group had similar second years survival (60% and 59.3%, respectively) (p = 0.803). The frequency of neutropenia was significantly higher in the CROSS group compared to the FLOT group (p = 0.004.) Conclusion: Postoperative pathological response rate in the CROSS group was significantly higher compared to the FLOT group. CROSS and FLOT protocols contributed to survival similarly in patients with GEJ ADC, hematological side effects were more pronounced in patients receiving CRT. Key Words: GEJ cancer, Esophageal cancer, Cross, Flot.

Sunitinib or Pazopanib: Is There Any Difference Between Tyrosine Kinase Inhibitors in the Pre-Nivolumab Setting in Metastatic Renal Cell Carcinoma?

Introduction Treatment options for metastatic renal cell carcinoma disease have been improved in recent years. However, there is still no optimal treatment sequence or combination for metastatic disease. We aimed to investigate whether patients differed in terms of disease outcomes regarding pre-nivolumab tyrosine kinase inhibitors (TKIs). Material and methods The analysis of patients was performed after all cohorts were sub-grouped into two groups according to pre-nivolumab TKIs as following the sunitinib arm and the pazopanib arm. Result A total of 75 patients were included in this study. The median follow-up time was eight months for all cohorts. The objective response rate was statistically significantly higher in the pazopanib arm as compared to the sunitinib arm (56% vs 30%, p=0.02). Progression-free survival was significantly higher in pazopanib than sunitinib (10.3 months vs 5.3 months, p=0.02). Multivariate analysis revealed that pazopanib treatment was associated with better progression-free survival (HR: 0.44, 95 CI; 0.22-0.91, p=0.02). While the median overall survival for patients who had received sunitinib was 11.0 months, it has not been reached the median in the pazopanib arm (11.0 months vs NR, p=0.051). Discussion We demonstrated significantly better progression-free survival and a higher objective response rate with nivolumab treatment in patients who had received pazopanib as compared with patients who received sunitinib in the pre-nivolumab period.

Can neutrophil/lymphocyte ratio be used as an indicator of inflammation in patients with hyperthyroidism?

BACKGROUND: In our study, we aimed to evaluate changes in the neutrophil and lymphocyte series and investigate whether the neutrophil/lymphocyte ratio (NLR) is indicative of inflammations in patients with hyperthyroidism. METHODS: A total of 161 patients were enrolled, 121 of which had hyperthyroidism (71 Graves' Disease (GD) and 50 non-Graves hyperthyroidism (NGH) patients) and 40 of which were control group members. Retrospectively, patients' neutrophil and lymphocyte counts were taken, and the NLR was calculated. RESULTS: While the number of neutrophils was significantly lower in the GD group (p = 0.003), there was no significant difference between the NGH and the control group. In the GD group, NLR values were significantly lower than the other two groups (median 1.39 for GD, median 1.84 for NGH and median 1.83 for the control group, p < 0.001). Only three patients in the GD group had neutropenia. There was also a significant negative correlation between free T3 and neutrophil count and NLR in hyperthyroid patients (r = -0.28, p = 0.001 and r = -0.34, p < 0.001, respectively). CONCLUSIONS: In our study, we found that NLR did not in crease in hyperthyroid patients and that this ratio decreased due to the decrease in neutrophil levels in GD. We thus concluded that NLR is not a suitable indicator of hyperthyroidism.