Beyond traditional therapies: clinical significance of complex molecular profiling in patients with advanced solid tumours-results from a Turkish multi-centre study.

OBJECTIVE: The objective of this multi-centre, real-world study was to examine the potential influence of comprehensive molecular profiling on the development of treatment decisions or adjustments for patients with advanced solid malignancies. We then evaluated the impact of these informed choices on patient treatment outcomes. METHODS: The study encompassed 234 adult patients (mean age: 52.7 ± 14.3 years, 54.7% women) who were diagnosed with solid tumours at 21 different medical centres in Turkey. Remarkably, 67.9% of the patients exhibited metastasis at the time of diagnosis. We utilized an OncoDNA (Gosselies, Belgium) platform (OncoDEEP) integrating next-generation sequencing with additional tests to harvest complex molecular profiling data. The results were analyzed in relation with two specific outcomes: (i) the impact on therapeutic decisions, including formulation or modifications, and (ii) associated treatment response. RESULTS: Out of the 228 patients with final molecular profiling results, 118 (50.4%) had their treatment modified, whilst the remaining 110 (47.0%) did not. The response rates were comparable, with 3.9 versus 3.4% for complete response, 13.6 versus 29.3% for partial response, 66.9 versus 51.7% for progressive disease and 15.5 versus 15.5% for stable disease for treatments informed and not informed by complex molecular profiling, respectively (P = 0.16). CONCLUSION: Our real-world findings highlight the significant impact of complex molecular profiling on the treatment decisions made by oncologists for a substantial portion of patients with advanced solid tumours. Regrettably, no significant advantage was detected in terms of treatment response or disease control rates.

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.

Contribution of "complete response to treatment" to survival in patients with unresectable metastatic colorectal cancer: A retrospective analysis.

BACKGROUND: The aim of the study is to reveal the contribution of complete response (CR) to treatment to overall survival (OS) in patients with unresectable metastatic colorectal cancer. In addition, to evaluate progression-free survival (PFS) in patients who attained CR to treatment and to examine the clinicopathologic features of the patient group with CR. METHODS: This article is a retrospective chart review. Patients diagnosed with metastatic colorectal cancer were divided into two groups. The systemic treatment was compared with the patients who received a full response according to the Response Evaluation Criteria in Solid Tumors (RECIST1.1) and those who did not attain CR (progression partial response and stable response) in terms of both PFS and OS data, and the effect of attaining CR to treatment on prognosis was evaluated. RESULTS: A total of 222 patients were included in the study. 202 of 222 patients could be evaluated in terms of complete response. All data from their files were tabulated and analyzed retrospectively. The mean age of diagnosis of the study group was 60.13 ± 12.52 years. The total number of patients who attained CR to treatment was 31 (15.3%); 171 (84.6%) patients did not attain CR. Patients who had a CR had longer median PFS times than patients who did not have a CR (15.2 vs. 7.4 months, P<0.001). Patients who had CR had longer median survival times than patients who did not have a CR (39.2 vs. 16.9 months, P<0.001). In subgroup patients who underwent primary surgery, the number of patients who attained CR was statistically higher compared with the number of patients who did not attain CR (p<0.001). Complete response was less common in the presence of liver metastasis and bone metastasis (p = 0.041 and p = 0.046, respectively), had a negative prognostic effect. In other words, 89.1% of patients with liver metastasis, 100.0% of patients with bone metastasis, and 88.7% of those who died did not have a CR to the treatment. According to multivariate analysis, CR to treatment, primary surgery, first-line chemotherapy (combination compared with fluoropyrimidine), and no bone metastasis were found to be predictors for OS. CONCLUSION: Providing CR with systemic treatment in patients with unresectable metastatic colorectal cancer (mCRC) contributes to prognosis. The primary resection in our secondary acquisitions from the study, the number of metastatic regions and the combination therapy regimens also contributed to the prognosis.

Avelumab Versus Docetaxel in Patients With Platinum-Treated Advanced NSCLC: 2-Year Follow-Up From the JAVELIN Lung 200 Phase 3 Trial.

INTRODUCTION: In the JAVELIN Lung 200 trial, avelumab (anti-programmed death-ligand 1 [PD-L1] antibody) did not significantly prolong overall survival (OS) versus docetaxel in patients with platinum-treated PD-L1+ NSCLC. We report greater than 2-year follow-up data. METHODS: Patients with stage IIIB or IV or recurrent NSCLC with disease progression after platinum-doublet chemotherapy were randomized 1:1 to avelumab 10 mg/kg every 2 weeks or docetaxel 75 mg/m2 every 3 weeks. The primary end point was OS in patients with PD-L1+ tumors (greater than or equal to 1% tumor cell expression; IHC 73-10 pharmDx assay). RESULTS: Of 792 patients, 529 had PD-L1+ tumors (264 versus 265 in the avelumab versus docetaxel arms, respectively). As of March 4, 2019, median duration of follow-up for OS in the PD-L1+ population was 35.4 months in the avelumab arm and 34.7 months in the docetaxel arm; study treatment was ongoing in 25 (9.5%) versus 0 patients, respectively. In the PD-L1+ population, 2-year OS rates (95% confidence interval [CI]) with avelumab versus docetaxel were 29.9% (24.5%-35.5%) versus 20.5% (15.6%-25.8%); in greater than or equal to 50% PD-L1+ subgroups, 2-year OS rates were 36.4% (29.1%-43.7%) versus 17.7% (11.8%-24.7%) and in the greater than or equal to 80% subgroup were 40.2% (31.3%-49.0%) versus 20.3% (12.9%-28.8%), respectively. Median duration of response (investigator assessed) was 19.1 months (95% CI: 10.8-34.8) versus 5.7 months (95% CI: 4.1-8.3). Safety profiles for both arms were consistent with the primary analysis. CONCLUSIONS: Although the JAVELIN Lung 200 primary analysis (reported previously) revealed that avelumab did not significantly prolong OS versus docetaxel in patients with platinum-treated PD-L1+ NSCLC, posthoc analyses at 2 years of follow-up revealed that 2-year OS rates were doubled with avelumab in subgroups with higher PD-L1 expression (greater than or equal to 50% and greater than or equal to 80%).

The Relationship Between Nutritional Status, Performance Status, and Survival Among Pancreatic Cancer Patients.

Aim: The purpose of this study was to identify the nutritional and performance status of Pancreatic Cancer (PanCa) patients and to determine the relationship between these parameters and their survival time.Material and Methods: Ninety-six PanCa patients [59.6% F, 61.4% M; mean age: 60.7 (min:28, max:80) years] were followed up for 6-24 months. The Patient Generated Subjective Global Assessment (PG-SGA) and Eastern Comparative Oncology Group (ECOG) scale were performed. Anthropometric measurements [height, weight, mid-upper arm circumference (MUAC), calf circumference (CC) and triceps skin fold thickness (TSF)], hand grip strength (HGS) were recorded. Survival analyses were conducted using Kaplan-Meier curves.Results: Malnutrition was observed in 85.5% (n = 82) and 54.2% of all patients had poor performance status. A positive correlation was observed between malnutrition and ECOG scale of the patients (P < .01). Antropometric measurements for women and men, respectively, were 34.4 ± 3.03-34.6 ± 3.43 cm for CC; 26.9 ± 3.47-26.05 ± 3.37 cm for MUAC; 20.5 ± 6.3-13.02 ± 7.7 mm for TSF; - 31.02 ± 7.64-20.13 ± 6.04 kg for HGS. Survival time of patients with SGA-A and B was 38.0 ± 6.6 months and of those with SGA-C was 12.0 ± 3.1 months (P = .000).Conclusion: Malnutrition negatively affected both performance status and survival time among PanCa patients.

Programmed cell death ligand-1 expression in gastroenteropancreatic neuroendocrine tumors.

PURPOSE: Gastroenteropancreatic tumors (GEPNETs) is a heterogeneous disease with variable clinical course. While promising therapeutic options exist for other adult cancers, there are no new molecular-based treatments developed for GEPNETs. One of the main targets of cancer immunotherapy is the Programmed Cell Death Ligand-1 (PD-L1) pathway. Our purpose was to investigate the profile of PD-L1 expression in different organs of GEPNETs and compare the conventional immunohistochemistry (IHC) with the RNA expression analysis via real time polymerase chain reaction (RT-PCR) in order to determine which patients might be appropriate for immune check point-targeted therapy. METHODS: A total of 59 surgically or endoscopically resected GEPNET tissues were retrospectively collected. The expression of PD-L1 and mRNA was evaluated with IHC. RESULTS: The expression of PD-L1 was significantly associated with the high-grade classification (p=0.012). PD-L1 mRNA expression in tumor samples appeared to be higher compared to the corresponding normal tissues. In appendix, stomach and small intestine, the expression of PD-L1 mRNA was higher in the tumor tissues compared to the respective controls. In pancreas and colon, control tissues tend to have a higher PD-L1 mRNA expression compared to tumor tissues. PD-L1 mRNA expression was higher in GEP carcinomas (p=0.0031). CONCLUSION: RT-PCR was found to be more sensitive in detecting PD-L1 expression than conventional IHC. This study may provide an important starting point and useful background information for future research about immunotherapy for appendix, stomach and small intestine neuroendocrine carcinomas.

Evaluation of sarcopenia, sarcopenic obesity, and phase angle in geriatric gastrointestinal cancer patients: before and after chemotherapy

Background/aim: The purpose of this study was to determine sarcopenia, sarcopenic obesity and phase angle (PA) and the influence of chemotherapy (CT) on anthropometric measurements and and the PA in in geriatric patients with gastrointestinal (GI) cancer. Materials and methods: The anthropometric measurements, calf circumference (CC), upper midarm circumference (UMAC), and hand grip strength (HGS), have been measured to understand muscle function of 153 patients (mean age of 70.5 ± 5.6 years, 28.8% female, 71.2% male). Sarcopenia and PA measurements have been evaluated by bioelectrical impedance analyses. The same evaluations were checked again after 1 cycle of CT (min: 4, max: 6 weeks). Results: Patient population consisted of colorectal (51,6%), gastric (26.8%), pancreas (11.8%), liver (7.2%), and biliary tract cancer (2%). UMAC (28.5 ± 4.4 before, 28.1 ± 4.9, P = 0.034 after CT), and HGS measurements (27.5 ± 8.6 before, 26.8 ± 8.8 after CT, P = 0.007) have significantly decreased after CT. CC measurement < 31 cm at first visit was seen in 13.1% of patients, but the ratio raised to 20.3% after CT (χ², P = 0.003). Severe sarcopenia was determined in 33% of all patients, and 30.0% of them have been considered as sarcopenic obese. Conclusion: Sarcopenia and sarcopenic obesity were prevalent in this group patients. The CT caused a decrease in muscle functions, UMAC, and CC. Patients should be followed up carefully for sarcopenia, sarcopenic obesity, and nutritional aspect and it would be proper to intervene before sarcopenia has not occurred yet.

Biweekly cetuximab in combination with platinum and 5-fluorouracil in metastatic head and neck carcinoma.

BACKGROUND AND AIM: The combination of cetuximab with platinum and 5-fluorouracil (5-FU) chemotherapy prolongs survival in patients with metastatic or recurrent squamous-cell carcinoma of the head and neck (SCCHN). Biweekly (once in 2 weeks) administration of cetuximab requires fewer hospital visits and decreases treatment costs; therefore, it is more convenient both for the patients and for the healthcare providers. Here, we assessed the efficacy, safety, and tolerability of an alternative biweekly regimen of cetuximab in combination with platinum and 5-FU chemotherapy as a first-line treatment for these patients. METHODS AND MATERIALS: Medical records of patients with metastatic or recurrent non-nasopharyngeal SCCHN who were treated with a biweekly regimen of cetuximab (500 mg/m2 on day 1), cisplatin (40 mg/m2 on day 1) or carboplatin (target area under the curve 3.5 mg/ml × min on day 1), folinic acid (400 mg/m2 on day 1), and 5-FU (400 mg/m2 bolus on day 1 followed by continuous infusion of 2,400 mg/m2 5-FU over 46 h) were retrospectively reviewed. Survival estimates were calculated with the Kaplan-Meier method. RESULTS: In total, 60 patients were included. The median age of the patients was 60.5. The objective response rate was 53.3% (95% confidence interval [CI] = 40.7-65.9). The median progression-free survival duration was 6.8 months (95% CI = 5.5-8.1) and the median overall survival duration was 13.3 months (95% CI = 8.4-18.2). The most common grade 3 or 4 adverse events were neutropenia (28.3%) and leucopenia (13.3%). Grade 3 or 4 rash was observed in 3.3% of the patients. CONCLUSION: Biweekly administration of cetuximab, cisplatin, and 5-FU is an effective regimen with a favorable toxicity profile for the first-line treatment of metastatic or recurrent SCCHN. These results warrant further evaluation of this regimen in prospective trials.

The Impact of Subtype Distribution in Inflammatory Breast Cancer Outcome.

OBJECTIVE: Inflammatory breast cancer (IBC) has an unfavourable prognosis despite the advances made in the treatment of breast cancer. Our study aimed to define immunohistochemistry-based surrogate subtype distribution to determine whether the breast cancer subtype accompanied survival outcome differences in IBC. MATERIALS AND METHODS: Medical records of female breast cancer patients with non-metastatic inflammatory breast cancer admitted to our clinic between March 2000 and December 2015 were retrospectively reviewed. Patient demographics, clinical and pathological feature of the primary tumour, adjuvant treatment options and survival data were analysed. Intrinsic breast cancer subtypes were defined according to ER, PR, HER-2 and ki-67 status. RESULTS: We identified 129 non-metastatic inflammatory breast cancer patients. Median follow-up was 73 months. 10 (7.7%) were luminal A-like, 67 (51.9%) were luminal B-like, 37 (28.6%) were HER-2 positive, and 15 (11.6%) were triple negative (TNBC) by immunohistochemistry. There were no statistically significant differences between subtypes in terms of histological type, grade, tumour size and lymph node status. Median disease-free survival was 47 months (95% confidence interval [CI] 29.2-82.6) and median overall survival was 75 months (95% CI 64.7-90.8). Triple negative breast cancer showed poorer outcome than other subgroups. Presence of TNBC disease was associated with poorer outcome compared to luminal A (HR: 0.19, 95% CI 0.04-0.92, p: 0.039), luminal B (HR: 0.34, 95% CI 0.15-0.74, p: 0.007) and HER-2 positive subgroups (HR: 0.40, 95% CI 0.17-0.94, p:0.037). Luminal A patients had a trend to have a better overall survival which did not reach to a statistical significant difference. CONCLUSION: Our study put forth that IBC have a poor prognosis irrespective of breast cancer surrogate subtype distribution. Luminal A, the most frequent subtype of breast cancer was the least common in our IBC patient group. TNBC had the worst outcome when compared to other breast cancer subtypes.

Avelumab versus docetaxel in patients with platinum-treated advanced non-small-cell lung cancer (JAVELIN Lung 200): an open-label, randomised, phase 3 study.

BACKGROUND: Antibodies targeting the immune checkpoint molecules PD-1 or PD-L1 have demonstrated clinical efficacy in patients with metastatic non-small-cell lung cancer (NSCLC). In this trial we investigated the efficacy and safety of avelumab, an anti-PD-L1 antibody, in patients with NSCLC who had already received platinum-based therapy. METHODS: JAVELIN Lung 200 was a multicentre, open-label, randomised, phase 3 trial at 173 hospitals and cancer treatment centres in 31 countries. Eligible patients were aged 18 years or older and had stage IIIB or IV or recurrent NSCLC and disease progression after treatment with a platinum-containing doublet, an Eastern Cooperative Oncology Group performance status score of 0 or 1, an estimated life expectancy of more than 12 weeks, and adequate haematological, renal, and hepatic function. Participants were randomly assigned (1:1), via an interactive voice-response system with a stratified permuted block method with variable block length, to receive either avelumab 10 mg/kg every 2 weeks or docetaxel 75 mg/m2 every 3 weeks. Randomisation was stratified by PD-L1 expression (≥1% vs <1% of tumour cells), which was measured with the 73-10 assay, and histology (squamous vs non-squamous). The primary endpoint was overall survival, analysed when roughly 337 events (deaths) had occurred in the PD-L1-positive population. Efficacy was analysed in all PD-L1-positive patients (ie, PD-L1 expression in ≥1% of tumour cells) randomly assigned to study treatment (the primary analysis population) and then in all randomly assigned patients through a hierarchical testing procedure. Safety was analysed in all patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT02395172. Enrolment is complete, but the trial is ongoing. FINDINGS: Between March 24, 2015, and Jan 23, 2017, 792 patients were enrolled and randomly assigned to receive avelumab (n=396) or docetaxel (n=396). 264 participants in the avelumab group and 265 in the docetaxel group had PD-L1-positive tumours. In patients with PD-L1-positive tumours, median overall survival did not differ significantly between the avelumab and docetaxel groups (11·4 months [95% CI 9·4-13·9] vs 10·3 months [8·5-13·0]; hazard ratio 0·90 [96% CI 0·72-1·12]; one-sided p=0·16). Treatment-related adverse events occurred in 251 (64%) of 393 avelumab-treated patients and 313 (86%) of 365 docetaxel-treated patients, including grade 3-5 events in 39 (10%) and 180 (49%) patients, respectively. The most common grade 3-5 treatment-related adverse events were infusion-related reaction (six patients [2%]) and increased lipase (four [1%]) in the avelumab group and neutropenia (51 [14%]), febrile neutropenia (37 [10%]), and decreased neutrophil counts (36 [10%]) in the docetaxel group. Serious treatment-related adverse events occurred in 34 (9%) patients in the avelumab group and 75 (21%) in the docetaxel group. Treatment-related deaths occurred in four (1%) participants in the avelumab group, two due to interstitial lung disease, one due to acute kidney injury, and one due to a combination of autoimmune myocarditis, acute cardiac failure, and respiratory failure. Treatment-related deaths occurred in 14 (4%) patients in the docetaxel group, three due to pneumonia, and one each due to febrile neutropenia, septic shock, febrile neutropenia with septic shock, acute respiratory failure, cardiovascular insufficiency, renal impairment, leucopenia with mucosal inflammation and pyrexia, infection, neutropenic infection, dehydration, and unknown causes. INTERPRETATION: Compared with docetaxel, avelumab did not improve overall survival in patients with platinum-treated PD-L1-positive NSCLC, but had a favourable safety profile. FUNDING: Merck and Pfizer.

Can yoga have any effect on shoulder and arm pain and quality of life in patients with breast cancer? A randomized, controlled, single-blind trial.

OBJECTIVE: To examine the effects of yoga on shoulder and arm pain, quality of life (QOL), depression, and physical performance in patients with breast cancer. METHODS: This prospective, randomized study included 42 patients. The patients in Group 1 underwent a 10-week Hatha yoga exercise program. The patients in Group 2 were included in a 10-week follow-up program. Our primary endpoint was arm and shoulder pain intensity. RESULTS: The group receiving yoga showed a significant improvement in their pain severity from baseline to post-treatment, and these benefits were maintained at 2.5 months post-treatment. When compared to the control group, there were no statistically significant differences between the 2 groups with respect to the parameters assessed at the end of week 10. CONCLUSION: Yoga was an effective and safe exercise for alleviating shoulder and arm pain, which is a complication with a high prevalence in patients with breast cancer.

A national, multicenter, non-interventional, observational study on treatment patterns in patients with metastatic renal cell carcinoma in Turkey - NOTES study.

INTRODUCTION: The introduction of targeted therapies in renal cell carcinoma has significantly improved its prognosis and treatment outcomes in recent years. Such treatment options are targeted therapies of the vascular endothelial growth factor (VEGF) pathway and the mammalian target of the rapamycin pathway. With the use of tyrosine kinase inhibitors (TKIs) and mammalian target of the rapamycin inhibitors, overall survival has increased up to 2 years. In Turkey, due to applicable reimbursement conditions for patients with metastatic renal cell carcinoma (mRCC), interferon use is mandated as a first-line treatment, thus providing information on the use of everolimus only after initial interferon and second-line VEGF-targeted treatments such as VEGF-TKI. PATIENTS AND METHODS: To provide a first real-life data set in Turkey, we conducted a prospective, non-interventional, observational study and assessed the efficacy and safety of everolimus after two lines of treatment including interferon. A total of 100 patients with histologically confirmed mRCC were enrolled in the study from 11 centers between June 2012 and March 2014 (70 males and 30 females). Efficacy was assessed on the basis of progression-free survival and overall survival; safety of everolimus was assessed on the basis of adverse event occurrence. RESULTS: The study results showed that the median progression-free survival with everolimus treatment was 8.1 months (95% CI: 5.1-11.1) and the median overall survival was 17.6 months (95% CI: 10.1-25.1), thus indicating a better overall response based on survival durations than those from the randomized Phase III REnal Cell cancer treatment with Oral RAD001 given Daily study results (4.9 and 14.8 months, respectively). CONCLUSION: The study showed that everolimus treatment is a safe and effective treatment option in the treatment of mRCC after VEGF-TKI, with an acceptable safety and tolerability profile in real-life settings.

The effect of chemotherapy on nutritional status and weakness in geriatric gastrointestinal system cancer patients.

OBJECTIVES: Malnutrition is common in patients with geriatric gastrointestinal system (GIS) cancer. This study aimed to evaluate patients with geriatric GIS cancer in terms of nutritional status and weakness and determine the changes caused by chemotherapy (CT). METHODS: Patients with geriatric GIS cancer who received CT were included in the study. Their nutritional status was assessed with the Mini Nutritional Assessment, and weakness was assessed with the handgrip strength/body mass index ratio. After CT (minimum 4 wk and maximum 6 wk later), patients were assessed for the same parameters. RESULTS: A total of 153 patients aged ≥65 y (mean age, 70.5 ± 5.6 y; 44 female and 109 male) were evaluated. The population consisted of patients who were diagnosed with colorectal (51.6%), gastric (26.8%), pancreatic (11.8%), hepatic (7.2%), biliary tract (2%), and esophageal (0.7%) cancer. Of these patients, 37.9% were malnourished, 34.6% were at risk of malnutrition, and 27.5% were well nourished. After one course of CT, the frequency of malnutrition increased to 46.4% (P = 0.001). The patient groups with the highest rates of weakness were those who were diagnosed with biliary tract, hepatic, and colorectal cancer (33.3%, 27.3%, and 20%, respectively). Weakness was significantly increased after one course of CT in patients who received CT before (P = 0.039). CONCLUSIONS: Malnutrition and weakness were common in patients with geriatric GIS cancer, and even one course of CT worsened the nutritional status of the patients. Patients who have received CT previously should be carefully monitored for weakness.

Is neuropathic pain associated with cardiac sympathovagal activity changes in patients with breast cancer?

Objective Heart rate variability (HRV) is a good indicator of the autonomic nervous system (ANS) activity. A few studies have been conducted recently and have shown a relationship between reduced HRV and conditions that lead to neuropathic pain (NP). In this study, we aimed to investigate whether NP is associated with changes in cardiac sympathovagal activity in patients with breast cancer (BC). Methods We used the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) questionnaire to evaluate NP in 70 patients with BC. The patients were subjected to a 24-h Holter ECG monitorization to determine heart rate variability (HRV). Standard deviation (SD) of the normal-to-normal RR intervals (SDNN), SD of the mean of the RR intervals (SDAAN), mean of the SD of the NN interval (SDNN Index), low-frequency component/high-frequency component ratio (LF/HF), and the mean heart rate of the patients were recorded. Results According to the LANSS questionnaire, 18 (25.7%) of the patients were classified as NP (+). The SDNN (P = 0.001), SDAAN (P = 0.003), and SDDN index (P = 0.007) were significantly lower in patients with NP than in patients without NP, whereas LF/HF ratio (P = 0.000) and mean heart rate were found to be significantly higher in patients with NP (P = 0.006). Conclusion According to our findings, NP (+) patients with BC had increased cardiac sympathetic activity, which was suggested to be associated with increased cardiovascular morbidity and mortality.

Risk factors for poor mobilization in solid tumors: How effectively can we mobilize patients with solid tumors?

BACKGROUND: In the literature, risk factors for poor mobilization were tried to identify. However, most of the studies consisted heterogeneous group of patients including both hematologic and oncologic malignancies. In this study, we aimed to identify the risk factors for poor mobilization in adults with solid tumors. METHODS: We enrolled 49(47 men, 2 women) adult patients with solid tumor who were mobilized between September 2007 and February 2017. All the mobilization procedures were performed with G-CSF(10µg/kg/day) with chemotherapy. Mobilization insufficiency was defined as peripheral blood CD34+stem cell number less than 10/µl and/or total collected CD34+cells less than 2.5×10 6/kg. RESULTS: The patients were divided into two groups, patients with successful mobilization at the first attempt(group 1, 36 patients,73.5%) and poor mobilizers (group 2, 13 patients 26.5%). Second and third mobilization attempt was needed in 11 and 2 patients, respectively. The median number of CD34+cells collected was 7,08×106/kg(0,6-19) with a median 4(1-6) apheresis. There was no statistical difference between two groups in terms of patient's and mobilization characteristics. Only number of CD 34+stem cells collected was statistically different (median 9,07×106/kg CD34+cells in group 1 versus 2,14×106/kg in group 2, p<0.05). The only possible risk factor that we could define was presence of organ metastasis. CONCLUSIONS: Since several methods and new drugs are available for peripheral stem cell collecting, risk factors should be identified clearly in adult population with solid tumors. So multicenter studies should be constructed for resolving this problem.

Pazopanib: a novel treatment option for aggressive fibromatosis.

BACKGROUND: Aggressive fibromatosis (AF), also known as desmoid tumor, is an uncommon soft tissue neoplasm. AF does not metastasize, but it is locally invasive and its propensity for recurrence after conservative resection is well documented. No effective cytotoxic treatment has been reported, hence there is a need for novel treatment strategies. CASE PRESENTATION: We present the case of an AF successfully treated with an oral tyrosine kinase inhibitor, pazopanib, with mild side effects. As far as we know, this is the first case of AF with complete response to pazopanib. CONCLUSION: Pazopanib might be an effective treatment option for AF.

Reliability and validity of the Turkish version of the EORTC QLQ-C15-PAL for patients with advanced cancer.

OBJECTIVE: Assessing quality of life, which is the main focus of palliative care, is highly important. The number of available, specific, simple, and valid assessment instruments for patients with advanced cancer in Turkey is limited. The aim of our study was to perform a psychometric evaluation of the Turkish version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 15-PAL (EORTC QLQ-C15-PAL). METHOD: The study was conducted in Izmir with patients who had received treatment in the palliative care unit of a university hospital between November of 2011 and December of 2013. Sociodemographic and disease characteristics forms, the Karnofsky Performance Status (KPS) Scale, and the EORTC QLQ-C15-PAL Scale were employed in order to gather data. RESULTS: A total of 150 patients completed the study: 55.3% of participants were female, 80.7% were married, and the average age was 52.76 ± 14.55. The value of Cronbach's α in the analyses ranged from 0.93 to 0.98. Most questionnaire areas had low to moderate correlations with the others. The moderate correlations were between fatigue and physical function (-0.41) and between insomnia and emotional function (-0.53). Conversely, weak correlations were found between nausea/vomiting and appetite loss (0.31) and between insomnia and pain (0.22). KPS scores decreased, patient physical and emotional function were diminished, global QoL declined, and patients' symptoms became more frank. SIGNIFICANCE OF RESULTS: We concluded that the EORTC QLQ-C15-PAL is a valid and reliable tool to determine the quality of life of advanced cancer patients who are undergoing palliative treatment in Turkey.

Combination of zoledronic acid and serine/threonine phosphatase inhibitors induces synergistic cytotoxicity and apoptosis in human breast cancer cells via inhibition of PI3K/Akt pathway.

The aim of this study was to investigate the cytotoxic and apoptotic effects of zoledronic acid (ZA) in combination with serine/threonine protein phosphatase inhibitors, calyculin-A (CA) and okadaic acid (OA), in human MCF-7 and MDA-MB-231 breast cancer cells. XTT cell viability assay was used to evaluate cytotoxicity. DNA fragmentation and caspase-3/7 activity assays were performed to evaluate apoptosis. Activities of phosphatase 1 (PP1) and phosphatase 2A (PP2A) were measured by serine/threonine phosphatase ELISA kit. Expression levels of PI3K, p-PI3K, Akt, p-Akt, Bcl-2, p-Bcl-2, Bad, and p-Bad proteins were evaluated by Western blot analysis. Combination of ZA with either CA or OA showed synergistic cytotoxicity and apoptosis as compared to any agent alone in both MCF-7 and MDA-MB-231 breast cancer cells. Combination treatment also resulted in inhibition of both PP1 and PP2A activities. Both agents used alone or in combination did not induce significant changes in total PI3K, Akt, Bcl-2, and Bad expressions, while p-PI3K, p-Akt, p-Bcl-2, and p-Bad levels were reduced by the combination treatment as compared to agents alone. Moreover, apoptotic effect of combination treatment was significantly inhibited in the presence of LY294002, a specific PI3K inhibitor, in both breast cancer cell lines. In conclusion, synergistic apoptotic effect of the combination treatment is correlated with the block of the PI3K/Akt signal pathway in breast cancer cells.

Adjuvant chemotherapy may contribute to an increased risk for metabolic syndrome in patients with breast cancer.

PURPOSE: Cytotoxic treatment may cause weight gain and important alterations in the metabolic status of breast cancer (BC) patients. The aim of this study was to investigate the changes in metabolic and anthropometric parameters of patients with BC who received adjuvant chemotherapy. METHODS: All consecutive women treated with adjuvant TAC (docetaxel 75 mg/m(2), doxorubicine 50 mg/m(2), cyclophosphamide 500 mg/m(2)) chemotherapy for node-positive breast carcinoma at our Institution between 2008 and 2010 were included. RESULTS: Among 104 patients, 84 of them were stage II and 20 of them were stage III. When we compared the measurements between 1(st) and 6(th) adjuvant chemotherapy, we observed statistically significant increases in weight and serum triglyceride levels, and decreases in high density lipoprotein, apolipoprotein A-1, transferrin, albumin and prealbumin levels. An elevation of follicle stimulating hormone, luteinizing hormone together with the decrease of estradiol was detected. Waist-to-hip ratio has also increased significantly. In subgroup analyses, we observed dramatic changes in body mass index in pre-menopausal women whereas no significant change was seen in the post-menopausal group. CONCLUSIONS: Adjuvant chemotherapy may contribute to an increased risk for metabolic syndrome in patients with BC and these changes are more profound in pre-menopausal patients.

Octreotide in combination with AT-101 induces cytotoxicity and apoptosis through up-regulation of somatostatin receptors 2 and 5 in DU-145 prostate cancer cells.

Prostate cancer (PCa) is the most common type of cancer among males. Although survival rate of early-stage PCa is high, treatment options are very limited for recurrent disease. In this study, the possible synergistic cytotoxic and apoptotic effect of octreotide in combination with AT-101 was investigated in DU-145 hormone and drug refractory prostate cancer cell line. To enlighten the action mechanisms of the combination treatment, expression levels of somatostatin receptors 2 and 5 (SSTR2 and SSTR5) were also investigated. Cell viability was measured by XTT assay. Apoptosis was assessed through DNA fragmentation analysis and caspase 3/7 assay. mRNA and protein levels of SSTR2 and SSTR5 were evaluated by qRT-PCR and western blot analysis, respectively. Octreotide in combination with AT-101 inhibited cell viability and induced apoptosis synergistically in DU-145 cells as compared to any agent alone. Combination treatment increased both SSTR2 and SSTR5 mRNA and protein levels in DU-145 cells. The data suggest that this combination therapy may be a good candidate for patients with advanced metastatic PCa do not respond to androgen deprivation.