The Comparison of FLOT and DCF Regimens as Perioperative Treatment for Gastric Cancer.

INTRODUCTION: Locoregional gastric cancer is a still serious problem and perioperative treatments may improve success of management. Different regimens were examined. The present study purposed to compare efficacy of FLOT and DCF regimens. METHODS: Retrospective multicenter study assesed the patients with locoregional gastric cancer. There are 240 patients (137 DCF, 103 FLOT). Survival rates were compared. RESULTS: Demographic features were similar between two groups, but time period was different. FLOT group had 7.8% pathological complete response, while DCF group did not have. Disease-free survival was longer in FLOT than DCF group (median not reached-13.94 months respectively). Median overall survival was similar (30.9 vs 37.8 months) but median follow-up affected the analysis. Survival for 36 months was 63% for FLOT and 40% for DCF group (p=0.015). CONCLUSION: FLOT regimen was superior on DCF regimen for response and survival rates. DCF is historical approach. Long term follow up period needed for FLOT treatment.

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.

Efficacy and safety of bevacizumab in patients with low-grade serous ovarian cancer.

Aim: To investigate the efficacy and safety of bevacizumab in patients with recurrent low-grade serous ovarian carcinoma. Materials & methods: The data of patients who received at least two cycles of bevacizumab in combination with chemotherapy were retrospectively recorded. Results: The median age of 51 patients was 56 (range: 33-75) years. The complete response rate was 10.4% and the partial response rate was 43.7%. The objective response rate was 54.1%. Median progression-free survival was 15.9 months (95% CI: 9.1-22.6) and median overall survival was 42.5 months (95% CI: 37.2-47.8). Conclusion: Bevacizumab with chemotherapy is an effective option for treating recurrent ovarian low-grade serous carcinoma.

Prognostic factors in non-metastatic HER2 'low' and HER2 'negative' breast cancer: single institute experience.

AIM: Comparison of prognosis and survival in human epidermal growth factor receptor 2 (HER2)-low and HER2-negative patients with early stage or locally advanced, hormone receptor-positive breast cancer. MATERIAL AND METHODS: In a retrospective single center study, the patients with early stage or locally advanced stage, hormone receptor (HR)-positive [estrogen receptor (ER) ≥ 1% and/or progesterone receptor (PR) ≥ 1%] and HER2 negative or HER2 low invasive breast cancer diagnosis were included. A total of 444 patients were included in the study. Patients were divided into two groups: HER2 negative and HER2 low. There were 235 (53%) patients in the HER2 negative group and 209 (47%) patients in the HER2 low group. RESULTS: The HER2 low group had significantly longer 5­year disease-free survival (DFS) than the HER2 negative group. The patients with lower Ki67 (< 20%) also had a longer 5­year DFS. CONCLUSION: Nonmetastatic HR+/HER2 low breast cancer patients had better DFS than HR+/HER2 negative ones. The Ki67 level and HER2 low status were independent prognostic factors. Randomized clinical trials are needed in early stage HER2 low breast cancer patients.

Higher TP53 somatic mutation prevalence from liquid biopsy analysis in ever smoker non-small-cell lung cancer patients.

OBJECTIVE: Cigarette smoking is a primary risk factor, linked to 80% of LC deaths. TP53, a key gene, is implicated in various cancers, with TP53 alterations in 36.7% of cancers. This research aims to investigate TP53 mutations detected in NSCLC patients by liquid biopsy and explore the relationship between these mutations and smoking history. MATERIAL AND METHOD: The study enrolled a total of 340 patients diagnosed with non-small cell lung cancer (NSCLC). For sequencing, the Illumina NextSeq 500 system was utilized. The oncogenicity of the variants was assessed according to the ClinGen/CGC/VICC SOP and the variants were categorized into four tiers according to AMP/ASCO/CAP. RESULTS: The most common mutations were in TP53 (48.7%), followed by EGFR, PIK3CA, and PTEN. Missense mutations were frequent, with TP53 and EGFR having higher rates in ever-smokers. No indels or complex mutations were found in ever-smokers. Patient age ranged from 20 to 86 years. Tier I-II variants were more common in ever-smokers, while Tier III variants were prevalent in never-smokers. TP53 mutations were more frequent in ever-smokers, showing a strong association with smoking. Domain distribution showed differences in PIK3CA. Transversion/transition ratios varied by gene and smoking status. DISCUSSION: The presence of TP53 mutations is strongly associated with both cigarette smoking and elevated Tv/Ti ratios. The tier status of TP53, EGFR, and PTEN variants does not show a specific domain distribution, but interesting associations are observed between the tier status and domain distribution in PIK3CA variants. Therefore, further comprehensive investigations are needed to explore this entity, as well as the underlying factors contributing to the increased Tv/Ti rates in the TP53 gene. Such research will provide deeper insights into the genetic alterations associated with smoking and tumor heterogeneity, ultimately aiding in the development of targeted therapies.

Simple and easily accessible prognostic markers in ewing sarcoma; neutrophil-lymphocyte ratio, neutrophil-platelet score and systemic-inflammation index.

Background: Inflammation markers are the new point of view in cancer due to increasing data on the interaction of immune system with tumor cells and their prognostic and predictive importance were found in many different types of solid tumors. Therefore, we aimed to evaluate the prognostic value of neutrophil-lymphocyte ratio (NLR), neutrophil-platelet score (NPS), and systemic inflammation index (SII) in Ewing sarcoma patients in which risk groups are still not clearly defined. Methods and Results: A total of 64 patients were evaluated retrospectively. Receiver operating characteristic analysis was performed to find cut-off values for NLR and SII. Survival analysis was calculated by using Kaplan-Meier method. Cox regression analysis was performed to determine prognostic factors such as age, stage, and neoadjuvant chemotherapy were statistically significant prognostic factors for OS in multivariate analysis. While patients with low NLR and SII had longer OS (P = 0.003 and P = 0.018), patients with high NPS score had shorter OS (67.7 vs 21.7 months, P = 0.001). Conclusion: Patients with lower NLR, NPS, and SII score have a better prognosis compared with those with higher NLR, NPS, and SII score and these simple parameters may be monitoring tools of the tumor microenvironment.

The Prognostic and Functional Impact of Sprouty 2 Expression in Non-small Cell Lung Cancer.

OBJECTIVE: We represent Sprouty 2 (Spry2) expression analysis and its association with key driver mutations and clinical features of patients with non-small cell lung cancer as the largest ex vivo data. METHODS: The strength of Spry2 expression was evaluated using the immunoreactivity score (IRS), which was calculated using the following formula: IRS=(staining intensity score) SI×(percentage of positively stained cells) PP. The median IRS score was defined as the cutoff value. Patients were grouped as "weak immunoreactivity score" (IRS: 0 to 4) or "strong immunoreactivity score" (IRS: ≥4) with respect to the IRS score. RESULTS: The intensity and percentage of Spry2 staining were significantly lower in tumor tissues than in normal lung tissues ( P <0.0001). Patients' characteristics were similar for both groups, except for smoking status and, brain and lymph node metastasis. Overall survival of patients with a strong immunoreactivity score was significantly lower than those with a weak immunoreactivity score among metastatic patients (6.9 mo vs. 13.6, P =0.023) and adenocarcinoma histology (7.0 mo vs. not reached, P =0.003). CONCLUSION: Spry2 expression was lower in tumor tissues than in normal lung parenchyma. Increased expression of Spry2 is associated with poor prognosis. There were no significant associations between epidermal growth factor receptor, anaplastic lymphoma kinase, or c-ros oncogene 1 rearrangement and Spry2 expression. Despite the absence of KRAS mutational analysis, the clinical and epidemiological features of patients suggested that KRAS mutation might be an underlying determinant factor of the functional role of Spry2 in non-small cell lung cancer.

Efficacy of adjuvant CDK4/6 inhibitors in hormone receptor-positive breast cancer: a systematic review and meta-analysis.

BACKGROUND: The combination of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors and standard endocrine therapy (ET) in the adjuvant treatment of hormone receptor (HR)-positive/HER2-negative breast cancer (BC) has yielded conflicting results. We performed a pooled analysis of the adjuvant efficacy of CDK4/6 inhibitors by including data from the NATALEE trial, the most recent trial on this topic. METHODS: We searched major databases and congress proceedings until 7 June 2023 to identify randomized controlled trials (RCT) comparing adjuvant CDK4/6 inhibitor plus ET combination versus ET in HR-positive/HER2-negative early-stage BC. RESULTS: Four RCTs involving a total of 17,749 patients were included. According to the pooled analysis of these four studies, significant improvement in invasive disease-free survival (iDFS) was observed with the addition of CDK4/6 inhibitors to standard ET (HzR: 0.81, 95% CI 0.67-0.97). IDFS benefit was irrespective from menopausal status, Ki-67 index, tumor grade, and previous chemotherapy. CDK4/6 inhibitors plus ET had a significant improvement in iDFS in stage 3 whereas there was a trend toward better iDFS in stage 2 (HzR for stage 3: 0.67, 95% CI 0.58-0.78; HzR for stage 2: 0.74, 95% CI 0.55-1.01). CONCLUSIONS: Addition of CDK4/6 inhibitors to standard ET in the adjuvant treatment of HR-positive/HER2-negative early-stage BC improves iDFS.

HIPEC in Ovarian Cancer: When and to Whom?

OBJECTIVE: To evaluate the optimal candidates for hyperthermic intraperitoneal chemotherapy (HIPEC) and cytoreductive surgery (CRS) in ovarian cancer. STUDY DESIGN: Descriptive study. Place and Duration of the Study: Health Sciences University, Dr. Abdurrahman Yurtasian Ankara Oncology Training and Research Hospital, Ankara, Turkey, between 2013 and 2021. METHODOLOGY: Ovarian cancer patients who underwent HIPEC and CRS for peritoneal involvement were included in this study. Thermosolutions were prepared as a closed system by using HT 2000 hyperthermic perfusion device. Then, cisplatin was applied at 100 mg/m2 at 42-42.5 °C for 60 minutes after CRS. RESULTS: A total of 47 patients were enrolled. The median age was 54 years (27-80) at the time of diagnosis. Forty (85.1%) patients had high grade serous carcinoma and 22 (46.7%) patients had clinical stage 3C disease. The median peritoneal cancer index (PCI) was 13 (3-24) in the whole population. HIPEC was applied as first-line treatment in 25 (51%) patients. Eleven (23.4%) patients had HIPEC in the post-neoadjuvant interval whereas 10 (21.3%) patients had it in platinum sensitive relapse. Median progression free survival (PFS) was 31(95% CI:11-50), 33 (95% CI:1-67), and 18 (95% CI:8-27) months in the primary, post-neoadjuvant interval, and platinum-sensitive relapse HIPEC groups, respectively. The patients with lower PCI (PCI<13) had significantly better OS than others with higher PCI (PCI>13, 145 months versus 42 months, p=0.034). CONCLUSION: HIPEC with CRS should be considered in selected serous carcinoma patients with peritoneal involvement, especially for the patients with primary ovarian cancer with lower PCI (PCI<13). KEY WORDS: Ovarian cancer, HIPEC, Peritoneal cancer index.

Uncommon variants detected via hereditary cancer panel and suggestions for genetic counseling.

OBJECTIVE: Hereditary cancer syndromes constitute 5-10% of all cancers. The development of next-generation sequencing technologies has made it possible to examine many hereditary cancer syndrome-causing genes in a single panel. This study's goal was to describe the prevalence and the variant spectrum using NGS in individuals who were thought to have a hereditary predisposition for cancer. MATERIAL AND METHOD: Analysis was performed for 1254 who were thought to have a familial predisposition for cancer. We excluded 46 patients who were carrying BRCA1/2 variants in this study, for focusing on the rare gene mutations. Sequencing was performed using the Sophia Hereditary Cancer Solution v1.1 Panel and the Qiagen Large Hereditary Cancer Panel. The Illumina MiSeq system was used for the sequencing procedure. The software used for the data analyses was Sophia DDM and QIAGEN Clinical Insight (QCITM) Analyze. The resulting genomic changes were classified according to the current guidelines of ACMG/AMP. RESULTS: Pathogenic/likely pathogenic variants were detected in 172 (13.7%) of 1254 patients. After excluding the 46 BRCA1/2-positive patients, among the remaining 126 patients; there were 60 (4.8%) breast cancer, 33 (2.6%) colorectal cancer, 9 (0.7%) ovarian cancer, 5 (0.4%) endometrium cancer, 5 (0.4%) stomach cancer, 3 (0.2%) prostate cancer patients. The most altered genes were MUTYH in 27 (2.1%) patients, MMR genes (MLH1, MSH6, MSH, MSH2, PMS2 and EPCAM) in 26 (2%) patients, and ATM in 25 (2%) patients. We also examined the genotype-phenotype correlation in rare variants. Additionally, we identified 11 novel variations. CONCLUSION: This study provided significant information regarding rare variants observed in the Turkish population because it was carried out with a large patient group. Personalized treatment options and genetic counseling for the patients are therefore made facilitated.

Relationship of The Characteristic Imaging Findings of Breast Cancer with Molecular Subtypes in Young Women.

BACKGROUND: The characteristic imaging findings of breast cancer in young women are not yet fully understood. It causes a delay in diagnosis by mixing with benign findings. OBJECTIVE: To evaluate the relationship between the imaging and histopathological features of breast cancer in women aged under 40 years. METHODS: In our center, 537 suspicious lesions were detected in a total of 15,223 adult female patients under 40 years who were evaluated by breast ultrasonography (US). As a result of the mammographic, histopathological, and immunohistochemical analysis, 101 lesions meeting the study criteria were included in the sample. RESULTS: The luminal subtypes of breast cancer mostly visualized as irregularly shaped spiculated lesions with calcification and architectural distortion mammography and presented as masses that were sometimes accompanied by increased echogenicity in the surrounding tissue on US. The human epidermal growth factor receptor 2 (HER2) enriched subtypes mostly had microlobulated or indistinct margins with heterogeneous echoes accompanied by high calcification on mammography. The triple-negative (TN) subtypes generally appeared as microlobulated lesions with angular or indistinct margins, hypo echogenicity, posterior enhancement or shadowing, and vascularization. CONCLUSION: Some radiological features of breast cancer in young women were found to be associated with molecular subtypes similar to other age groups in the literature. However, unlike other age groups, the incidences of the HER2-enriched subtype presenting with only calcification, TN subtypes presenting with circumscribed masses, and calcification were found to be low among the young women in our study.

Gemcitabine-associated digital necrosis in metastatic breast cancer.

INTRODUCTION: Gemcitabine is a nucleoside analog antimetabolite used in various malignancies, including metastatic breast cancer. Objective response rates in its use as a single agent in the treatment of metastatic breast cancer are not to be underestimated. Cutaneous, hematological, pulmonary, and vascular side effects are well-known side effects. Venous thromboembolism may occur with antineoplastics, such as platinum compounds. Arterial thromboembolism is rare in cancer, almost rare with chemotherapy. Here, we present a metastatic breast cancer patient who had digital necrosis due to arterial occlusion with gemcitabine monotherapy. CASE REPORT: A 54-year-old metastatic breast cancer female patient had digital ischemia and necrosis in the left hand's fifth finger after the second course of single-agent gemcitabine as the fourth line setting. Gemcitabine was discontinued, and medical treatment was started. Thrombus was detected in the left subclavian artery digital angiography. Balloon angioplasty and stenting were applied. However, digital amputation had to be performed since tissue necrosis had not regressed despite radiological interventions and medical treatment. MANAGEMENT AND OUTCOME: Gemcitabine was discontinued. Low molecular weight heparin and acetylsalicylic acid were started. The distal phalanx was amputated due to necrosis during follow-up. Gemcitabine was permanently stopped. DISCUSSION: Gemcitabine-related vascular events, including arterial thrombosis, may also occur in cancer patients, especially those with higher tumor burden. Therefore, predisposing factors for hypercoagulability and vascular occlusion should be questioned in more detail even before starting antineoplastics which are known to have a lower risk for thrombosis, such as gemcitabine monotherapy.

Is the serum level of survivin, an antiapoptotic protein, a potential predictive and prognostic biomarker in metastatic pancreatic cancer?

In the present study, we aimed to assess the association between the serum survivin level and overall survival and treatment response rates in metastatic pancreatic cancer (MPC). Serum samples were prospectively collected from 41 patients with newly diagnosed MPC patients and 41 healthy individuals (control group) to assess the survivin levels. The median survivin level was 136.2 ng/mL in patients with MPC and 52 ng/mL in healthy individuals (P = .028). Patients were divided into low- and high-survivin groups according to the baseline median survivin level. Patients with a high serum survivin level compared with a low serum survivin level had shorter median progression-free survival (2.39 vs 7.06 months; P = .008, respectively) and overall survival (3.74 vs 9.52 months; P = .026, respectively). Patients with higher serum survivin levels had significantly worse response rates (P = .007). The baseline high level of serum survivin in patients with MPC may be associated with treatment resistance and poor prognosis. A confirmation will be needed for these results in future large multicenter prospective studies.

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.

Real life experience of patients with locally advanced gastric and gastroesophageal junction adenocarcinoma treated with neoadjuvant chemotherapy: a Turkish oncology group study.

Neoadjuvant chemotherapy (NACT) in gastroesophageal junction (GEJ) and gastric cancer (GC) was shown to improve survival in recent studies. We aimed to share our real-life experience of patients who received NACT to compare the efficacy and toxicity profile of different chemotherapy regimens in our country. This retrospective multicentre study included locally advanced GC and GEJ cancer patients who received NACT between 2007 and 2021. Relation between CT regimens and pathological evaluation were analysed. A total of 794 patients from 45 oncology centers in Turkey were included. Median age at the time of diagnosis was 60 (range: 18-86). Most frequent NACT regimens used were FLOT (65.4%), DCF (17.4%) and ECF (8.1%), respectively. In the total study group, pathological complete remission (pCR) rate was 7.2%, R0 resection rate 86.4%, and D2 dissection rate was 66.8%. Rate of pCR and near-CR (24%), and R0 resection (84%) were numerically higher in FLOT arm (p > 0.05). Patients who received FLOT had also higher chemotherapy-related toxicity rate compared to patients who received other regimens (p > 0.05). Median follow-up time was 16 months (range: 1-154 months). Estimated median overall survival (OS) was 58.4months (95% CI: 35.2-85.7) and disease-free survival (DFS) was 50.7 months (95% CI: 25.4-75.9). The highest 3-year estimated OS rate was also shown in FLOT arm (68%). We still do not know which NACT regimen is the best choice for daily practice.  Clinicians should tailor treatment regimens according to patients' multifactorial status and comorbidities for to obtain best outcomes. Longer follow-up period needs to validate our results.

Prognostic factors of perioperative FLOT regimen in operable gastric and gastroesophageal junction tumors: real-life data (Turkish Oncology Group).

BACKGROUND: Perioperative FLOT regimen is a standard of care in locally advanced operable gastric and GEJ adenocarcinoma. We aimed to determine the efficacy, prognostic factors of perioperative FLOT chemotherapy in real-life gastric and GEJ tumors. METHODS: The data of patients who were treated with perioperative FLOT chemotherapy were retrospectively analyzed from 34 different oncology centers in Turkey. Baseline clinical and demographic characteristics, pretreatment laboratory values, histological and molecular characteristics were recorded. RESULTS: A total of 441 patients were included in the study. The median of age our study population was 60 years. The majority of patients with radiological staging were cT3-4N(+) (89.9%, n = 338). After median 13.5 months (IQR: 8.5-20.5) follow-up, the median overall survival was NR (95% CI, NR to NR), and median disease free survival was 22.9 (95% CI, 18.6 to 27.3) months. The estimated overall survival at 24 months was 62%. Complete pathological response (pCR) and near pCR was achieved in 23.8% of all patients. Patients with lower NLR or PLR have significantly longer median OS (p = 0.007 and p = 0.033, respectively), and patients with lower NLR have significantly longer median DFS (p = 0.039), but PLR level did not affect DFS (p = 0.062). The OS and DFS of patients with better ECOG performance scores and those who could receive FLOT as adjuvant chemotherapy instead of other regimens were found to be better. NLR was found to be independent prognostic factor for OS in the multivariant analysis. At least one adverse event reported in 57.6% of the patients and grade 3-4 toxicity was seen in 23.6% patients. DISCUSSION: Real-life perioperative FLOT regimen in operable gastric and GEJ tumors showed similar oncologic outcomes compared to clinical trials. Better performance status, receiving adjuvant chemotherapy as same regimen, low grade and low NLR and PLR improved outcomes in real-life. However, in multivariate analysis, only NLR affected OS.

Predictive and prognostic effect of ABO blood group on immune checkpoint inhibitors.

BACKGROUND: The relationship of the ABO blood group system with the immune response is known, but its relationship with immune checkpoint inhibitors (ICIs) has not been clearly investigated until now. OBJECTIVE: In this study, the relationship between different blood groups and nivolumab treatment response in patients with advanced malignant melanoma was investigated. METHODS: The data of patients who used nivolumab for advanced malignant melanoma between April 2018 and April 2021 were retrospectively reviewed. RESULTS: A total of 73 patients were included in the study. In the progression-free survival (PFS) analysis according to blood groups, it was 3.9 months, 16.1 months, 20.0 months and 3.0 months for A, B, AB and O, respectively (p= 0.1). Overall survival (OS) analysis according to blood groups was 5.1 months, 25.0 months, 20.0 months and 9.3 months for A, B, AB and O, respectively (p= 0.1). The B antigen group (B or AB) had significantly longer PFS and OS than the non-B antigen group (A or O) (16.1 vs. 3.5 months for PFS, respectively, p= 0.03; 20.0 vs. 7.4 months for OS, respectively, p= 0.02). CONCLUSIONS: The presence of B antigen provides a significant advantage in terms of survival in patients using ICIs for advanced melanoma.

Real-Life Analysis of Efficacy and Safety of Everolimus Plus Exemestane in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor-2-Negative Metastatic Breast Cancer Patients: A Turkish Oncology Group (TOG) Study.

PURPOSE: This study evaluated the efficacy and safety of everolimus (EVE) plus exemestane (EXE) in hormone-receptor positive (HR+), human epidermal growth factor receptor-2-negative (HER2-) metastatic breast cancer (MBC) patients in real-life settings. METHODS: Overall, 204 HR+, HER2- MBC patients treated with EVE + EXE after progressing following prior endocrine treatment were included. Overall survival (OS) and progression-free survival (PFS) and safety data were analyzed. RESULTS: The objective response rate, median PFS, and median OS were 33.4%, 8.9 months, and 23.4 months, respectively. Multivariate analysis revealed that negative progesterone receptor status was a significant determinant of poor treatment response (p = 0.035) and PFS (p = 0.024). The presence of bone-only metastasis was associated with better treatment response (p = 0.002), PFS (p < 0.001), and OS (p = 0.001). CONCLUSION: We confirmed the favorable efficacy and safety profile of EVE + EXE for HR+, HER - MBC patients.

The Relationship Between Plexin C1 Overexpression and Survival in Hepatocellular Carcinoma: a Turkish Oncology Group (TOG) Study.

PURPOSE: Plexin C1 is a transmembrane receptor and plexin C1 overexpression might have role in carcinogenesis. Hepatocellular carcinoma (HCC) has poor prognosis because of its aggressive behavior and limited treatment options, especially in advanced stage. We recently documented that Plexin C1 was overexpressed in HCC. We aimed to evaluate the prognostic significance of Plexin C1 overexpression in HCC in the present study. METHODS: Plexin C1 overexpression was evaluated immunohistochemically on paraffin-embedded blocks of the HCC patients. Plexin C1 immunohistochemical staining was scored. Plexin C1 overexpression staining intensity and prevalence were used for plexin scale staining evaluation and plexin scores were estimated according this staining scale. Plexin C1 score and its association with survival and clinicopathological features was assessed. RESULTS: Sixty-seven HCC patients with adequate tissue for pathological evaluation were included. Median age was 63 years with male predominance (male to female ratio was 4.75 (n 57/12). Well-differentiated HCC (53.7%) patients had higher plexin C1 overexpression (p < 0.05). Median OS was 22.1 months. Patients with lower plexin C1 score (< 12) had shorter OS (17.5 vs 30.1 months, p = 0.036). Neutrophil count, GGT, and PNR (platelet/neutrophil ratio) had prognostic significance (p = 0.047, p = 0.018, and p = 0.045). CONCLUSION: Plexin C1 overexpression is inversely correlated with grade in HCC. The patients with lower rate of Plexin C1 overexpression have worse survival outcome. It might be a prognostic factor in HCC.