Efficacy of first-line CDK 4-6 inhibitors in premenopausal patients with metastatic breast cancer and the effect of dose reduction due to treatment-related neutropenia on efficacy: a Turkish Oncology Group (TOG) study.

The only phase 3 study on the effectiveness of CDK 4-6 inhibitors in first-line treatment in premenopausal patients with hormone receptor (HR) positive, HER2 negative metastatic breast cancer is the MONALEESA-7 study, and data on the effectiveness of palbociclib is limited. Data are also limited regarding the effectiveness of CDK 4-6 inhibitors in patients whose dose was reduced due to neutropenia, the most common side effect of CDK 4-6 inhibitors. In our study, we aimed to evaluate the effectiveness of palbociclib and ribociclib in first-line treatment in patients with premenopausal metastatic breast cancer and the effect of dose reduction due to neutropenia on progression-free survival. Our study is a multicenter, retrospective study, and factors affecting progression-free survival (PFS) were examined in patients diagnosed with metastatic premenopausal breast cancer from 29 different centers and receiving combination therapy containing palbociclib or ribociclib in the metastatic stage. 319 patients were included in the study. The mPFS for patients treated with palbociclib was 26.83 months, and for those receiving ribociclib, the mPFS was 29.86 months (p = 0.924). mPFS was 32.00 months in patients who received a reduced dose, and mPFS was 25.96 months in patients who could take the initial dose, and there was no statistical difference (p = 0.238). Liver metastasis, using a fulvestrant together with a CDK 4-6 inhibitor, ECOG PS 1 was found to be a negative prognostic factor. No new adverse events were observed. In our study, we found PFS over 27 months in patients diagnosed with premenopausal breast cancer with CDK 4-6 inhibitors used in first-line treatment, similar to post-menopausal patients. We did not detect any difference between the effectiveness of the two CDK 4-6 inhibitors, and we showed that there was no decrease in the effectiveness of the CDK 4-6 inhibitor in patients whose dose was reduced due to neutropenia.

Prognostic significance of 18F-FDG PET/CT indices in metastatic renal cell cancer and evaluation of revised IMDC risk model by including 18F-FDG PET-CT parameters.

BACKGROUND: Prognostic markers in metastatic renal cell cancer (mRCC) are still insufficient. Any prognostic model objectively determines disease burden. PURPOSE: To investigate the relationship between 18-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) parameters and outcomes in mRCC, and to define a revised International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model for the intermediate-risk group. MATERIAL AND METHODS: A retrospective study of mRCC was conducted. To investigate the prognostic significance of 18F-FDG PET/CT parameters, maximum standardized uptake value (SUVmax), total lesion glycolysis (TLG), and metabolic tumor volume (MTV) were determined in pre-treatment images. Cutoff values were defined by ROC curve analyses and their association with outcomes was analyzed. Additionally, a TLG-adjusted IMDC model was created by stratifying intermediate-risk group patients according to TLG levels. RESULTS: The study included 52 patients. The disease control rate (DCR) was 61.5% and median overall survival (OS) was 18 months (95% confidence interval=9.2-25.8). In the univariate analyses, IMDC score, MTV, and TLG were prognostic factors for Disease Control Rate (DCR), and Eastern Cooperative Oncology Group (ECOG)-Performance Status (PS), IMDC score, lactate dehydrogenase (LDH), treatment option, MTV, and TLG were prognostic factors for OS (P < 0.05 each). In the multivariate analyses, MTV was an independent prognostic factor for DCR, and ECOG-PS, LDH, IMDC score, and TLG were independent prognostic factors for OS. According to the revised-IMDC model, the intermediate-favorable group showed longer OS than the intermediate-unfavorable group. CONCLUSION: Pretreatment MTV was independent prognostic factor for DCR and ECOG-PS, LDH, IMDC score, and TLG were independent prognostic factors for OS. Revised-IMDC model could identify patients with a worse prognosis among the IMDC intermediate-risk group.

Tailored total neoadjuvant therapy for locally advanced rectal cancer: One size may not fit for all!

While current neoadjuvant protocols have proven benefits on local control for majority of patients with locally advanced rectal cancer, there are certain clinical conditions that require future advances for improving the outcomes. Total neoadjuvant therapy incorporates systemic chemotherapy planned within standard neoadjuvant protocols either before or after radiotherapy for locally advanced rectal cancer as a whole. Enhanced compliance with planned oncological therapy, tumour downstaging, administration of chemotherapy at the earliest time in the disease course to help assessing chemosensitivity are the proposed benefits of total neoadjuvant therapy in patients with locally advanced rectal cancer. Patient selection criteria for administration of total neoadjuvant therapy in the recent guidelines are unclear. Since current literature is inconclusive for the optimal sequence and type of radiotherapy and chemotherapy, premature incorporation of total neoadjuvant therapy for all locally advanced rectal cancers may result in overtreatment and subsequently toxicity. This article aims to discuss the current literature and to propose a future perspective by considering real-life scenarios reflecting patients' needs for treatment of locally advanced rectal cancer.

The alterations of serum FGF-21 levels, metabolic and body composition in early breast cancer patients receiving adjuvant endocrine therapy.

BACKGROUND: In early breast cancer patients, the effects of hormonal therapy (tamoxifen and aromatase inhibitors) on plasma fibroblast growth factor 21 (FGF-21), lipid levels and body composition have not yet been investigated. Therefore, we aimed to analyze the relationship between FGF-21 and body composition as well as the effects of tamoxifen and aromatase inhibitors on plasma lipid levels, FGF-21, and body composition. METHODS: A total of 72 patients were treated with either tamoxifen or aromatase inhibitors due to their menopausal status after adjuvant radiotherapy. Each patient was followed-up over a period of 1 year. Changes in body composition and serum lipid profile, glucose and FGF-21 levels were evaluated. We recorded the type of hormonal therapy, body mass index, waist-to-hip ratio, lipid profile, and FGF-21 levels both at the beginning and after 12 months. RESULTS: There was a statistically significant decrease in serum FGF-21 levels after 12 months of adjuvant endocrine therapy (46 ± 19.21 pg/ml vs. 30.99 ± 13.81 pg/ml, p< 0.001). Total body water (p< 0.001), serum glucose (p= 0.036) and triglyceride levels (p< 0.001) also exhibited a significant decrease. The decreases in total cholesterol and low-density lipoprotein were not statistically significant. Likewise, high-density lipoprotein increased after adjuvant endocrine therapy, although it did not reach statistical significance. The changes in body composition, glucose, lipid profile and FGF-21 were similar in tamoxifen and aromatase inhibitor groups. A positive correlation was found between basal weight, fat mass, fat-free mass and serum FGF-21 levels; however, the correlation was maintained only for the fat-free mass at the 12th month. CONCLUSION: As part of the present study, we suggest that both tamoxifen and aromatase inhibitors can reduce FGF-21 levels independently of body compositions, and these drugs can provide antihyperlipidemic, antidiabetic and cardio-protective effects. We also recommend that serum FGF-21 level can be utilized as a tumor biomarker in early-stage breast cancer and for monitoring purposes. FGF-21 levels may help physicians estimate prognosis, too. Further studies with larger populations may shed light on the role of FGF-21 in breast cancer.

The maximum standardized uptake value of metastatic site in 18 F-FDG PET/CT predicts molecular subtypes and survival in metastatic breast cancer: An Izmir Oncology Group study.

PURPOSE: The purpose of this study was to analyse the association between the 18F-2-deoxy-2-fluorodeoxyglucose maximum standardized uptake value (SUVmax) of metastatic sites and molecular subtypes and survival in metastatic breast cancer (MBC) patients. METHODS: Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) was performed in 176 MBC patients before any therapeutic intervention. The FDG uptakes of metastatic sites were evaluated using the SUVmax. Histopathological prognostic parameters, such as the tumor size, grade, lymph node involvement, lymphovascular invasion, estrogen (ER), progesterone receptors (PR), HER2 status and Ki67 were determined from the primary breast tumor tissue. The SUVmax of the metastatic sites was assessed in relation to the molecular subtypes and survival in univariate and multivariate analyses. Cox regression analysis was used to evaluate the associations between SUVmax measurements and overall survival (OS). RESULTS: The mean SUVmax of 176 tumors was 8.0. Among the subtypes 49 (28.8%) were luminal A, 51 (28.9%) luminal B, 35 (19.8%) HER2-overexpressing, and 41 (23.2%) triple- negative, and the corresponding means of SUVmax were 5.6, 7.4, 11.4, 11.0, respectively. A cut-off value of ≤8.4 yielded 80% sensitivity and 57.1% specificity with an area under the receiver operating characteristics curve (AUC) of 0.731 for predicting that a tumor was of the luminal A subtype. A cut-off value of SUVmax ≥10.05 yielded 62.9% sensitivity and 67.4% specificity with an AUC of 0.648 for predicting a HER2 overexpressing subtype. A cut-off value of SUVmax ≥9.25 yielded 61% sensitivity and 64.4% specificity with an AUC of 0.660 for predicting a triple-negative subtype. The SUVmax could not effectively differentiate patients with luminal B subtype. Cox regression analysis showed that in patients with MBC, a SUVmax ≤7.55 acted as an independent negative prognostic factor for OS (hazard ratio/HR = 1.552). CONCLUSION: The SUVmax of metastatic sites on pretreatment 18F-FDG PET/CT may be an independent prognostic factor for the diagnosis of molecular phenotypes and survival in MBC patients.

The Effects of Adjuvant Endocrine Treatment on Serum Leptin, Serum Adiponectin and Body Composition in Patients with Breast Cancer: The Izmir Oncology Group (IZOG) Study.

BACKGROUND: A limited number of studies have been conducted on the effects of hormonal therapy with tamoxifen (TMX) or aromatase inhibitors (AIs) on plasma levels of leptin and adiponectin, as well as body composition in breast cancer (BC) patients. Therefore, we aimed to analyze the relationship between adipocytokines and body composition as well as the effects of TMX and AIs on plasma adiponectin, leptin, leptin/adiponectin ratio (LAR) and body composition. METHODS: Patients were treated with either TMX or AI according to their menopausal status after adjuvant radiotherapy. Changes in body composition and serum leptin and adiponectin levels were evaluated. We recorded the type of hormonal therapy, BMI, waist/hip ratio (WHR), leptin and adiponectin levels at study entry, and after 6 and 12 months. RESULTS: From baseline to the 6- and 12-month follow-ups, there were statistically significant increases in WHR (p = 0.003), fat mass (p = 0.041), and serum leptin (p < 0.001) and adiponectin levels (p < 0.001). The changes in body composition and serum leptin and adiponectin levels were similar in TMX and AI groups. A statistically significant decrease was found in total body water and LAR (p < 0.001). Although weight and body fat percentage increased, such increases were not statistically significant. A positive correlation was found between baseline BMI and serum leptin levels. This correlation was maintained at 6 and 12 months. The negative correlation found between serum adiponectin levels at baseline and baseline BMI did not last throughout the study. CONCLUSION: In this study, increased leptin and adiponectin levels and a decreased LAR were found in both AI and TMX groups. These changes might have occurred through both mechanisms of hormonal therapy and body composition changes. Therefore, AIs and TMX may exert their protective effects for BC patients by decreasing LAR rather than affecting leptin or adiponectin alone.

Quality of life in colorectal cancer patients: an Izmir Oncology Group (IZOG) study.

PURPOSE: To investigate the variables of quality of life (QoL) among Turkish patients with colorectal cancer (CRC). METHODS: In this prospective study we investigated the QoL of Turkish CRC patients. Two hundred and twenty two patients with CRC were included. The sociodemographic form and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) were used. RESULTS: The study group consisted of 142 males (64%) and 80 females (36%). The mean patient age was 55.68±11.387 years. The majority of the patients (36.9%) had local disease while advanced-stage disease and locally advanced stage disease had 32.2% and 28.8% of the patients; respectively. The mean QoL score was moderate (62.81± 27.0). The most common complaints were fatigue, economic difficulties and constipation. Gender, education level and disease stage were associated with QoL. Physical, role and social functioning were more adversely affected in female patients. Compared to women, men had significantly more favorable global QoL (p=0.044). Some functional scales were worse in advanced disease compared to other stages.These outcomes were statistically significant in the functional scales of global health (p=0.007), physical (p=0.03), cognitive (p=0.01) and emotional function (p=0.007). Patients with advanced disease had worse outcomes in some symptoms (nausea, vomiting, dyspnea, loss of appetite and financial distress). CONCLUSIONS: Female gender and advanced disease were strongly associated with poorer QoL among Turkish CRC patients.

Evaluation of c-kit (CD 117) expression as a prognostic factor in testicular germ cell tumors: an Izmir Oncology Group (IZOG) study.

PURPOSE: Despite the successful use of targeted and molecular therapies in other cancers, little progress has been made in the management of testicular germ cell tumors (TGCTs). c-kit (CD 117) is a good target for cancer treatment and possesses an impressive role in the current oncological practice. We aimed to evaluate c-kit expression in early stage TGCTs as a prognostic factor. METHODS: Patients with TGCTs who were referred to the Medical Oncology Clinic and underwent curative surgical operation were included in our study before starting chemo- therapy. Immunohistochemistry was performed on formalin-fixed and paraffin-embedded three-micrometer thick sections with CD 117 Rabbit Anti c-kit in vitro gene kit. Biochemically, we utilized AFP and ß-HCG Immunlite 2000 device with solid phase chemiluminescent immunometric method, and LDH Roche models with the DP-standardized UV method. AFP 0-15 ng/ml, ß-HCG < 0.1 mlu/ml and LDH 240-480 mg/dl were considered as normal values. RESULTS: Sixty-five patients were included in our study. Forty-one (63%) patients had non-seminoma tumors (NSGCTs) and 24 (37%) had seminoma. Statistically significant c-kit expression was found in patients with seminoma (p<0.0001). There was no difference between negative or positive c-kit expression in terms of clinicopathological characteristics, including preoperative serum levels of AFP, ß-HCG, LDH, lymph node involvement, distant metastasis, and IGCCCG risk classification. No correlation was found between these parameters and 5-year progression free survival (PFS) rate except for tumor stage, presence of lymph node metastasis and IGCCCG score (p=0.001, p=0.04, and p=0.0001, respectively). Five-year PFS rate of patients with positive CD 117 was 72.2% (95% CI, 54.6-89.8), and 56.6% (95% CI, 31.2-82.1) for those without CD 117 expression involvement (p=0.12). CONCLUSION: So far, there has been no significant breakthrough in the treatment of cisplatin-refractory TGCTs in the era of targeted therapies. No prognostic importance of c-kit expression has been found in our study. However, we believe that c-kit expression, in numerical terms, can be considered as a good prognostic factor for patients with TGCTs. The fact that all seminoma cases displayed positive c-kit expression is what we think has driven this result.

Sexual satisfaction, anxiety, depression and quality of life among Turkish colorectal cancer patients [Izmir Oncology Group (IZOG) study].

OBJECTIVE: Determination of psychological problems will shed light on the terms of solution and provide support to patients about these problems will ensure the patients' coherence to the treatment and will enhance the benefits they receive from treatment. In this study, we aimed to determine these psychosocial problems and the interactions with each other in colon cancer patients. METHODS: In this study, 105 patients with colorectal cancer were included. The forms consist of sociodemographic features, Hospital Anxiety and Depression Scale, European Organization for Research on Treatment of Cancer Questionnaires Quality of Life-C30 and Golombok-Rust Inventory of Sexual Satisfaction questionnaires. RESULTS: Male patients had significantly higher European Organization for Research on Treatment of Cancer Questionnaires Quality of Life-C30 function scales and global quality-of-life scores than female patients. Golombok-Rust Inventory of Sexual Satisfaction scores of female patients were significantly higher than that of male patients. European Organization for Research on Treatment of Cancer Questionnaires Quality of Life-C30 function scales and global quality-of-life scores of the patients with high depression scores were significantly lower, conversely symptom scale scores of the patients with high depression scores were significantly higher than that of the patients with low depression scores. Patients with low anxiety scores had significantly higher European Organization for Research on Treatment of Cancer Questionnaires Quality of Life-C30 function scales and global quality-of-life scores than the patients with high anxiety scores. Symptom scale scores of the patients with high anxiety scores were significantly higher than that of the patients with low anxiety scores. The scores of Golombok-Rust Inventory of Sexual Satisfaction except premature ejaculation and vaginismus were significantly higher in patients with high anxiety scores and a significant difference was determined in touch, avoidance and anorgasm. CONCLUSIONS: This study demonstrates that there is a significant association with anxiety/depression symptoms and quality-of-life scores, sexual dysfunction. Sexual dysfunction is significantly more common in patients with high anxiety and depression scores.

Sexual satisfaction, anxiety, depression and quality of life in testicular cancer survivors.

We aimed to investigate anxiety, depression and sexual satisfaction levels of testicular cancer survivors (TCSs) and compare the scores with healthy men's. The Hospital Anxiety and Depression Scale (HADS), Golombok-Rust Inventory of Sexual Satisfaction (GRISS) and European Organization for Research on Treatment of Cancer Questionnaires Quality of Life-C30 were used. Forty-one TCSs and thirty-eight healthy men were participated in this study. The total HADs scores of TCSs (12.21 ± 8.19) were less than the healthy group (14.44 ± 6.53; p > 0.05). The high depression scores rate was 29.2 and 55.2, and high anxiety scores rate was 24.4 and 28.9 for TCSs and healthy group, respectively. When we evaluated GRISS subscores and anxiety levels, we found significantly increase only in avoidance subscores in the TCSs (p = 0.04). When we evaluated GRISS subscores and depression levels, GRISS subscores of the TCSs who had high depression scores were also high. However, statistical significance was found in satisfaction (p = 0.009), touch (p = 0.04), avoidance (p = 0.01) and erectile dysfunction (p = 0.04) subscores in the TCSs. In the TCSs whose anxiety scores were high, emotional functioning (p = 0.009) and global QoL (p = 0.01) subscores of GRISS was found significantly low. In the TCSs whose depression scores were high, physical (p = 0.01), cognitive (p = 0.04), emotional (p = 0.03), social functioning (p = 0.02) and global QoL (p < 0.001) subscores of GRISS were found significantly low. Anxiety, depression and sexual satisfaction levels of TCSs were found to be similar with the control population.

Prognostic evaluation of breast cancer patients with evident bone marrow metastasis.

In this study, we aimed to evaluate the clinicopathologic characteristics and prognosis of breast cancer (BC) patients with symptomatic bone marrow metastasis (BMM). Fifty-four BC patients, including patients with and without BMM, were evaluated retrospectively. In particular, the clinicopathologic features and survival of the patients with BMM (n = 27) were assessed and compared with the patients without BMM. All of the patients with BMM also had osseous metastases, and bone was the first site for distant recurrence in the majority of patients in the study group. Anemia was the most frequent symptom at presentation. The median time to BMM was 36.1 months (range 1.6-70.5 months, 95% CI). HER2(+) patients developed BMM earlier than HER2(-) patients (3.2 versus 38.3 months, 95% CI; p = 0.05). Patients with advanced disease at the time of initial BC diagnosis developed BMM earlier than patients with early disease (p = 0.04). Time to development of BMM was significantly shorter in tumors with perinodal infiltration (p = 0.001) and multicentric focus (p = 0.025). Median survival time after the diagnosis of apparent BMM was 6.43 months. Survival after BMM diagnosis in patients with grade III tumors was significantly shorter than in patients with grade I-II tumors (1.43 versus 5.36 months, 95% CI; p < 0.001). Systemic therapy after BMM diagnosis significantly prolonged survival (17.3 versus 0.93 months, 95% CI; p < 0.001). Hormone receptor-positive, high-grade, advanced-stage tumors at the time of initial BC diagnosis were more common in patients with BMM. Invasive lobular histology was also more frequent in patients with BMM. In conclusion, the presence of hormone receptor-positive, multicentric, grade III, advanced-stage tumors may be important risk factors for the development of evident BMM in BC patients. Systemic single-agent chemotherapy can prolong survival in these patients. However, multicenter analyses are required to verify these findings.

The impact of cell proliferation markers and p53 mutation status on prognosis of non-metastatic colon cancer.

BACKGROUND AND OBJECTIVES: We aimed to evaluate the prognostic value of cell cycle proteins and p53 together with clinicopathologic features in non-metastatic resected colon cancer. METHODS: One hundred nine patients who were diagnosed with resected colon cancer between 2006 and 2011 were analyzed retrospectively. Immunohistochemical staining analyses were used to evaluate the expression of cyclins D1 and A, p53 and Ki-67 in tumor tissue. RESULTS: High cyclin D1 and cyclin A expression was more common in stage II than stage III tumors. Disease recurrence was more frequent in tumors with low cyclin D1 expression (P = 0.05). No significant association was observed between p53, Ki-67 or cyclin A expression and the risk of relapse and/or death. Multivariate analysis showed that the strongest predictor for a shorter disease-free survival period was extracapsular nodal invasion (ECNI). CONCLUSIONS: We were not able to establish a strong association between patient prognosis and cyclins D1 and A, p53 or Ki-67 expression. However, a negative correlation between cyclin D1 and cyclin A expression and disease stage as well as more frequent relapses in patients with low expression of cyclin D1 suggested that cyclins may be predictive for early relapse in non-metastatic colon cancer.

Depression, anxiety and sexual satisfaction in breast cancer patients and their partners-Izmir oncology group study.

BACKGROUND: We aimed to investigate anxiety, depression and sexual satisfaction levels and the effects of depression and anxiety upon the sexual satisfaction of Turkish breast cancer patients and their partners. MATERIALS AND METHODS: Data were collected from one hundred breast cancer patients and their partners, using three forms: one covering information about socio-demographic characteristics of the patients, the Hospital Anxiety and Depression Scale (HADs) and the Golombok-Rust Inventory of Sexual Satisfaction (GRISS). RESULTS: The frequencies, avoidance and touch subscores were statistically significantly high in the patients. Among those with high anxiety scores, the frequency, communication, satisfaction, touch, and anorgasmic subscale scores of GRISS were found to be significantly high. Among the partners whose anxiety scores were high, only the premature ejaculation subscale was statistically significant. It was determined that for partners with higher depression scores, the communication, satisfaction, avoidance, premature ejaculation and erectile dysfunction subscores of GRISS were statistically higher compared to partners with lower depression scores. CONCLUSIONS: Patients' quality of life may be increased by taking precautions to reduce their and their partners' psychosocial and psychosexual concerns.

Does immunohistochemistry provide additional prognostic data in gastrointestinal stromal tumors?

BACKGROUND: To investigate the predictive and prognostic effects of clinicopathologic and immunohistochemical (IHC) features in patients with gastrointestinal stromal tumours (GISTs). MATERIALS AND METHODS: Fifty-six patients who were diagnosed with GIST between 2002 and 2012 were retrospectively evaluated. Relationships between clinicopathologic/immunohistochemical factors and prognosis were investigated. RESULTS: Median overall survival (OS) of the whole study group was 74.9 months (42.8-107.1 months), while it was 95.2 months in resectable and 44.7 months in metastatic patients respectively (p=0.007). Epitheliolid tumor morphology was significantly associated with shortened OS as compared to other histologies (p=0.001). SMA(+) tumours were significantly correlated with low (<10/50HPF) mitotic activity (p=0.034). Moreover, SMA(+) patients tended to survive longer and had significantly longer disease-free survival (DFS) times than SMA (-) patients (37.7 months vs 15.9 months; p=0.002). High Ki-67 level (≥30%) was significantly associated with shorter OS (34 vs 95.2 months; 95%CI; p=0.001). CD34 (-) tumours were significantly associated with low proliferative tumours (Ki-67<%10) (p=0.026). Median PFS (progression-free survival) of the patients who received imatinib was 36 months (27.7-44.2 months). CD34 (-) patients had significantly longer PFS times than that of negative tumours; (50.8 vs 29.8 months; p=0.045). S100 and desmin expression did not play any role in predicting the prognosis of GISTs. Multivariate analysis demonstrated that ≥10/50HPF mitotic activity/HPF was the only independent factor for risk of death in GIST patients. CONCLUSIONS: Despite the negative prognostic and predictive effect of high Ki-67 and CD34 expression, mitotic activity remains the strongest prognostic factor in GIST patients. SMA positivity seems to affect GIST prognosis positively. However, large-scale, multicenter studies are required to provide supportive data for these findings.

Cisplatin plus gemcitabine for treatment of breast cancer patients with brain metastases; a preferential option for triple negative patients?

BACKGROUND: To assess the efficacy and tolerability of Cisplatin plus Gemcitabine combination in patients with brain metastases (BM) from breast cancer (BC). MATERIALS AND METHODS: Eighteen BC patients with BM who were treated with Cisplatin plus Gemcitabine regimen between 2003-2011 were evaluated. RESULTS: A median of 6 cycles of this regimen were received, in fifteen patients (83.3%) as first-line chemotherapy, in 2 as second- line and in 1 as third-line after diagnosis of BM. Dose reduction was performed in 11 (61.1%) patients; major reasons were neutropenia and leukopenia. Grade III neutropenia and Grade II trombocytopenia rates were 33.3% and 16.7% respectively. Overall response rate (ORR; complete+partial response rate) was 33.4% (n=6) for the entire study population; triple negative patients achieved an 66.6% ORR while hormone receptor (HR) positive patients had 25% and HER2 positive patients 12.5%. Median progression-free survival was 5.6 months (2.4-8.8 months, 95%CI) and longer in patients with triple negative breast cancer (TNBC) (median 7.4 months, 95%CI, 2.4-12.3 months) than the patients with other subtypes (median 5 months for HER2 positive and 3.6 months for HR positive patients). Median PFS of the patients with TNBC who received this regimen as first-line was 9.2 months (5.2-13.2 months, 95%CI). CONCLUSIONS: Cisplatin plus Gemcitabine may be a treatment option for patients with BM from breast cancer. Longer PFS and higher response rates are results that support the usage of this regimen especially for the triple negative subtype. However, further prospective and randomized trials are clearly required to provide more exact information.

Predictive and prognostic factors in locally advanced breast cancer: effect of intratumoral FOXP3+ Tregs.

This study aimed to investigate the prognostic and predictive effect of FOXP3+ Tregs together with clinicopathologic factors in locally advanced breast cancer (LABC) patients. The medical records of 101 LABC patients who received neoadjuvant chemotherapy (NAC) between 2005 and 2012 were evaluated retrospectively. The density of intratumoral FOXP3+ lymphocytes in paraffin-embedded tissues was assessed by immunohistochemical analyses in appropriate cases. The relationship with clinicopathologic features, prognosis and chemotherapy response was investigated. HR(-) and HER2(+) tumors tended to have higher pre-chemotherapy Tregs than HR(+) tumors, and significantly higher pathologic complete response (PCR) rates were observed in these patients. Treg decline after NAC was associated with better pathological response rates. Lower intratumoral infiltration of FOXP3+ Tregs after NAC (<3.4/HPF) was significantly associated with higher PCR rates for breast, and close to the significance limit for total (or both for breast and axillary) PCR rates (PCR for breast: 25 vs. 2.9 % for low vs. high Treg, p = 0.001; PCR for breast + axillary tissue: 13.9 vs. 0 %, p = 0.05). Despite better PCR rates, patients with high intratumoral Treg infiltrates (≥11.5/HPF) before chemotherapy had significantly shorter overall survival than patients with low Treg infiltrates (<11.5/HPF). Cox multivariate regression analyses demonstrated that the density of Treg infiltration before chemotherapy was the strongest predictor for survival. This study established the predictive and prognostic effect of intratumoral FOXP3+ Tregs in LABC patients. To predict clinical outcome, evaluation of FOXP3+ Tregs in tumoral tissues before and after NAC should be considered for these high-risk patients.

Malignant epithelioid hemangioendothelioma progressing after chemotherapy and Interferon treatment: a case presentation and a brief review of the literature.

Epithelioid hemangioendothelioma is a rare, low-grade malignant vascular tumour. It is frequently seen in the liver, but can occur in the lungs, bones, and other soft tissues. Although survival time might be reasonable in cases that can undergo liver transplantation, there is no consensus on the treatment of metastatic patients. We report a 24-year-old female patient with rapidly progressing malignant epithelioid hemangioendothelioma that presented with acute abdominal distension. The patient was refractory to anthracycline and Interferon treatment and died 6.5 months after the diagnosis.

The clinicopathological evaluation of the breast cancer patients with brain metastases: predictors of survival.

We aimed to define the clinicopathologic characteristics of breast cancer (BC) patients with brain metastasis (BM) and to investigate the effect of these parameters on survival. Seventy-nine patients diagnosed with BC and symptomatic BM between 1995 and 2011 were retrospectively evaluated. The relationship between clinicopathological features and outcome was investigated. Triple negative patients had the shortest overall survival (OS) while HR(+)HER2(-) patients had the longest (48.2  vs 88.2 months, 95 % CI; p = 0.33). Multivariate analysis demonstrated that luminal A subtype was the strongest positive predictor of prolonged OS (HR 0.48, 95 % CI 0.28-0.84; p = 0.01), while poor performance status (PS) (ECOG 3-4) at BM was the strongest predictor of shortened OS (HR 1.92, 95 % CI 1.21-3.06; p = 0.006). The patients with early-stage BC at diagnosis had BM later than the advanced-staged patients (47 months for Stage I-II disease, 23.2 months for Stage III-IV disease, 95 % CI; p = 0.002). Median survival after BM was 10.2 months (6.4-14 months, 95 % CI). The patients with liver or skin metastases had significantly shorter survival than the patients with only BM (4.8 vs 17 months, p < 0.001 for liver and 4.8 vs 11.1 months, p = 0.04 for skin). Multivariate analysis demonstrated that regardless of the BC subtype, lack of systemic therapy, and liver involvement were independent factors associated with increased risk of death (HR 4, 95 % CI 1.7-9.1; p = 0.001 and HR 2.2, 95 % CI 1.05-4.9; p = 0.036 respectively). Clinical outcome after BM mostly depends on the ECOG PS and the fact that whether the patient received systemic therapy or not. Systemic therapy prolongs survival especially in HER2 positive patients.

Metastases of renal cell carcinoma to the larynx and thyroid: Two case reports on metastasis developing years after nephrectomy.

Renal cell carcinoma (RCC) has a high metastatic potential due to its hematogen and vascular features. It metastasizes frequently to the lungs, the bones, the liver, the lymph nodes and the brain. Metastasis of RCC to the head and neck region is quite rare. In this case report, two RCC patients with head and neck metastases are presented: one occurring after 5 years and the other occurring 17 years after diagnosis.